Scholars@Duke
Douglas Alan Marchuk

Douglas Alan Marchuk

James B. Duke Distinguished Professor of Molecular Genetics and Microbiology
Molecular Genetics and Microbiology
douglas.marchuk@duke.edu
Duke Box 3175, Durham, NC 27710
213 Research Dr, 265 Clinical and Research Labs, Durham, NC 27710

Selected Publications

Somatic mutations in arteriovenous malformations in hereditary hemorrhagic telangiectasia support a bi-allelic two-hit mutation mechanism of pathogenesis.

Journal Article Am J Hum Genet · October 3, 2024 Hereditary hemorrhagic telangiectasia (HHT) is an inherited disorder of vascular malformations characterized by mucocutaneous telangiectases and arteriovenous malformations (AVMs) in internal organs. HHT is caused by inheritance of a loss of function mutat ... Full text Link to item Cite

Except for Robust Outliers, Rapamycin Increases Lesion Burden in a Murine Model of Cerebral Cavernous Malformations.

Journal Article Transl Stroke Res · July 9, 2024 Cerebral cavernous malformation (CCM) is a hemorrhagic cerebrovascular disease where lesions develop in the setting of endothelial mutations of CCM genes, with many cases also harboring somatic PIK3CA gain of function (GOF) mutations. Rapamycin, an mTORC1 ... Full text Link to item Cite

Pathologic features of brain hemorrhage after radiation treatment: case series with somatic mutation analysis.

Journal Article J Stroke Cerebrovasc Dis · July 2024 BACKGROUND: Radiation treatment for diseases of the brain can result in hemorrhagic adverse radiation effects. The underlying pathologic substrate of brain bleeding after irradiation has not been elucidated, nor potential associations with induced somatic ... Full text Link to item Cite

Brain AVM compactness score in children with hereditary hemorrhagic telangiectasia.

Journal Article Childs Nerv Syst · July 2024 OBJECTIVE: The brain arteriovenous malformation (BAVM) nidus compactness score (CS), determined on angiography, predicts BAVM recurrence after surgical resection among children with sporadic BAVMs. We measured the angiographic CS for BAVMs among children w ... Full text Link to item Cite

De Novo Brain Vascular Malformations in Hereditary Hemorrhagic Telangiectasia.

Journal Article Pediatr Neurol · June 2024 BACKGROUND: Approximately 10% of people with hereditary hemorrhagic telangiectasia (HHT) have brain vascular malformations (VMs). Few reports describe de novo brain VM formation. International HHT Guidelines recommend initial brain VM screening upon HHT di ... Full text Link to item Cite

Transcriptomic signatures of individual cell types in cerebral cavernous malformation.

Journal Article Cell Commun Signal · January 9, 2024 Cerebral cavernous malformation (CCM) is a hemorrhagic neurovascular disease with no currently available therapeutics. Prior evidence suggests that different cell types may play a role in CCM pathogenesis. The contribution of each cell type to the dysfunct ... Full text Link to item Cite

Single-nucleus DNA sequencing reveals hidden somatic loss-of-heterozygosity in Cerebral Cavernous Malformations.

Journal Article Nat Commun · November 2, 2023 Cerebral Cavernous Malformations (CCMs) are vascular malformations of the central nervous system which can lead to moderate to severe neurological phenotypes in patients. A majority of CCM lesions are driven by a cancer-like three-hit mutational mechanism, ... Full text Link to item Cite

mTORC1 Inhibitor Rapamycin Inhibits Growth of Cerebral Cavernous Malformation in Adult Mice.

Journal Article Stroke · November 2023 BACKGROUND: Cerebral cavernous malformations (CCMs) are vascular malformations that frequently cause stroke. CCMs arise due to loss of function in one of the genes that encode the CCM complex, a negative regulator of MEKK3-KLF2/4 signaling in vascular endo ... Full text Link to item Cite

Developmental expression of the Sturge-Weber syndrome-associated genetic mutation in Gnaq: a formal test of Happle's paradominant inheritance hypothesis.

Journal Article Genetics · August 9, 2023 Sturge-Weber Syndrome (SWS) is a sporadic (non-inherited) syndrome characterized by capillary vascular malformations in the facial skin, leptomeninges, or the choroid. A hallmark feature is the mosaic nature of the phenotype. SWS is caused by a somatic mos ... Full text Link to item Cite

Circulating Plasma miRNA Homologs in Mice and Humans Reflect Familial Cerebral Cavernous Malformation Disease.

Journal Article Transl Stroke Res · August 2023 Patients with familial cerebral cavernous malformation (CCM) inherit germline loss of function mutations and are susceptible to progressive development of brain lesions and neurological sequelae during their lifetime. To date, no homologous circulating mol ... Full text Link to item Cite

Cardiac Troponin I-Interacting Kinase Affects Cardiomyocyte S-Phase Activity but Not Cardiomyocyte Proliferation.

Journal Article Circulation · January 10, 2023 BACKGROUND: Identifying genetic variants that affect the level of cell cycle reentry and establishing the degree of cell cycle progression in those variants could help guide development of therapeutic interventions aimed at effecting cardiac regeneration. ... Full text Link to item Cite

Randomized, double-blind, placebo-controlled, crossover trial of oral doxycycline for epistaxis in hereditary hemorrhagic telangiectasia.

Journal Article Orphanet J Rare Dis · November 7, 2022 BACKGROUND: Vascular malformations in hereditary hemorrhagic telangiectasia (HHT) lead to chronic recurrent bleeding, hemorrhage, stroke, heart failure, and liver disease. There is great interest in identifying novel therapies for epistaxis in HHT given it ... Full text Link to item Cite

Genetic genealogy uncovers a founder deletion mutation in the cerebral cavernous malformations 2 gene.

Journal Article Hum Genet · November 2022 Cerebral cavernous malformations (CCM) are vascular malformations consisting of collections of enlarged capillaries occurring in the brain or spinal cord. These vascular malformations can occur sporadically or susceptibility to develop these can be inherit ... Full text Link to item Cite

A novel somatic mutation in GNAQ in a capillary malformation provides insight into molecular pathogenesis.

Journal Article Angiogenesis · November 2022 Sturge-Weber syndrome (SWS) is a sporadic, congenital, neuro-cutaneous disorder characterized by a mosaic, capillary malformation. SWS and non-syndromic capillary malformations are both caused by a somatic activating mutation in GNAQ encoding the G protein ... Full text Link to item Cite

A cross-species approach using an in vivo evaluation platform in mice demonstrates that sequence variation in human RABEP2 modulates ischemic stroke outcomes.

Journal Article Am J Hum Genet · October 6, 2022 Ischemic stroke, caused by vessel blockage, results in cerebral infarction, the death of brain tissue. Previously, quantitative trait locus (QTL) mapping of cerebral infarct volume and collateral vessel number identified a single, strong genetic locus regu ... Full text Open Access Link to item Cite

Rapamycin in Cerebral Cavernous Malformations: What Doses to Test in Mice and Humans.

Journal Article ACS Pharmacol Transl Sci · May 13, 2022 Cerebral cavernous malformations (CCMs) are hemorrhagic neurovascular lesions that affect more than 1 million people in the United States. Rapamycin inhibits CCM development and bleeding in murine models. The appropriate dosage to modify disease phenotype ... Full text Link to item Cite

Developmental venous anomalies are a genetic primer for cerebral cavernous malformations.

Journal Article Nat Cardiovasc Res · March 2022 Cerebral cavernous malformations (CCM) are a neurovascular anomaly that may occur sporadically, or be inherited due to autosomal dominant mutations in KRIT1, CCM2, or PDCD10. Individual lesions are caused by somatic mutations which have been identified in ... Full text Link to item Cite

Quantification metrics for telangiectasia using optical coherence tomography.

Journal Article Sci Rep · February 2, 2022 Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder that causes vascular malformations throughout the body. The most prevalent and accessible of these lesions are found throughout the skin and mucosa, and often rupture causing ble ... Full text Link to item Cite

Utility of modified Rankin Scale for brain vascular malformations in hereditary hemorrhagic telangiectasia.

Journal Article Orphanet J Rare Dis · September 19, 2021 BACKGROUND: Approximately 10% of hereditary hemorrhagic telangiectasia (HHT) patients harbour brain vascular malformations (VMs). Intracranial hemorrhage (ICH) from brain VMs can lead to death or morbidity, while treatment options for brain VMs also have a ... Full text Link to item Cite

Pilot investigation of circulating angiogenic and inflammatory biomarkers associated with vascular malformations.

Journal Article Orphanet J Rare Dis · September 3, 2021 BACKGROUND: Vascular malformations in the central nervous system are difficult to monitor and treat due to their inaccessible location. Angiogenic and inflammatory proteins are secreted into the bloodstream and may serve as useful biomarkers for identifyin ... Full text Link to item Cite

Cyclo-oxygenase 2, a putative mediator of vessel remodeling, is expressed in the brain AVM vessels and associates with inflammation.

Journal Article Acta Neurochir (Wien) · September 2021 BACKGROUND: Brain arteriovenous malformations (bAVM) may rupture causing disability or death. BAVM vessels are characterized by abnormally high flow that in general triggers expansive vessel remodeling mediated by cyclo-oxygenase-2 (COX2), the target of no ... Full text Link to item Cite

Cerebral Cavernous Malformation: From Mechanism to Therapy.

Journal Article Circ Res · June 25, 2021 Cerebral cavernous malformations are acquired vascular anomalies that constitute a common cause of central nervous system hemorrhage and stroke. The past 2 decades have seen a remarkable increase in our understanding of the pathogenesis of this vascular di ... Full text Link to item Cite

Multicenter Research Data of Epilepsy Management in Patients With Sturge-Weber Syndrome.

Journal Article Pediatr Neurol · June 2021 BACKGROUND: Epilepsy in typical Sturge-Weber syndrome (SWS) is common, and many questions remain regarding the treatment outcomes. We analyzed a large multicenter database with focus on neurological drug treatment in different demographic and SWS character ... Full text Link to item Cite

PIK3CA and CCM mutations fuel cavernomas through a cancer-like mechanism.

Journal Article Nature · June 2021 Vascular malformations are thought to be monogenic disorders that result in dysregulated growth of blood vessels. In the brain, cerebral cavernous malformations (CCMs) arise owing to inactivation of the endothelial CCM protein complex, which is required to ... Full text Link to item Cite

Propranolol inhibits cavernous vascular malformations by β1 adrenergic receptor antagonism in animal models.

Journal Article J Clin Invest · February 1, 2021 Propranolol, a pleiotropic β-adrenergic blocker, has been anecdotally reported to reduce cerebral cavernous malformations (CCMs) in humans. However, propranolol has not been rigorously evaluated in animal models, nor has its mechanism of action in CCM been ... Full text Link to item Cite

Predictors of mortality in patients with hereditary hemorrhagic telangiectasia.

Journal Article Orphanet J Rare Dis · January 6, 2021 BACKGROUND: Retrospective questionnaire and healthcare administrative data suggest reduced life expectancy in untreated hereditary hemorrhagic telangiectasia (HHT). Prospective data suggests similar mortality, to the general population, in Denmark's centre ... Full text Link to item Cite

A Neuroprotective Locus Modulates Ischemic Stroke Infarction Independent of Collateral Vessel Anatomy.

Journal Article Front Neurosci · 2021 Although studies with inbred strains of mice have shown that infarct size is largely determined by the extent of collateral vessel connections between arteries in the brain that enable reperfusion of the ischemic territory, we have identified strain pairs ... Full text Open Access Link to item Cite

Novel Murine Models of Cerebral Cavernous Malformations.

Journal Article Angiogenesis · November 2020 Cerebral cavernous malformations (CCMs) are ectatic capillary-venous malformations that develop in approximately 0.5% of the population. Patients with CCMs may develop headaches, focal neurologic deficits, seizures, and hemorrhages. While symptomatic CCMs, ... Full text Link to item Cite

Cerebral cavernous malformations are driven by ADAMTS5 proteolysis of versican.

Journal Article J Exp Med · October 5, 2020 Cerebral cavernous malformations (CCMs) form following loss of the CCM protein complex in brain endothelial cells due to increased endothelial MEKK3 signaling and KLF2/4 transcription factor expression, but the downstream events that drive lesion formation ... Full text Link to item Cite

Genotype-Phenotype Correlations in Children with HHT.

Journal Article J Clin Med · August 22, 2020 Hereditary hemorrhagic telangiectasia (HHT), a rare autosomal dominant disease mostly caused by mutations in three known genes (ENG, ACVRL1, and SMAD4), is characterized by the development of vascular malformations (VMs). Patients with HHT may present with ... Full text Link to item Cite

A Brain-Targeted Orally Available ROCK2 Inhibitor Benefits Mild and Aggressive Cavernous Angioma Disease.

Journal Article Transl Stroke Res · June 2020 Cavernous angioma (CA) is a vascular pathology caused by loss of function in one of the 3 CA genes (CCM1, CCM2, and CCM3) that result in rho kinase (ROCK) activation. We investigated a novel ROCK2 selective inhibitor for the ability to reduce brain lesion ... Full text Link to item Cite

Quality of Life in Children With Sturge-Weber Syndrome.

Journal Article Pediatr Neurol · December 2019 AIM: We assessed the utilization of the National Institutes of Health Quality of Life in Neurological Disorders (Neuro-QoL) in pediatric patients with Sturge-Weber syndrome, a rare neurovascular disorder which frequently results in seizures, brain atrophy, ... Full text Link to item Cite

Distinct cellular roles for PDCD10 define a gut-brain axis in cerebral cavernous malformation.

Journal Article Sci Transl Med · November 27, 2019 Cerebral cavernous malformation (CCM) is a genetic, cerebrovascular disease. Familial CCM is caused by genetic mutations in KRIT1, CCM2, or PDCD10 Disease onset is earlier and more severe in individuals with PDCD10 mutations. Recent studies have shown that ... Full text Link to item Cite

Somatic Mutations in Vascular Malformations of Hereditary Hemorrhagic Telangiectasia Result in Bi-allelic Loss of ENG or ACVRL1.

Journal Article Am J Hum Genet · November 7, 2019 Hereditary hemorrhagic telangiectasia (HHT) is a Mendelian disease characterized by vascular malformations (VMs) including visceral arteriovenous malformations and mucosal telangiectasia. HHT is caused by loss-of-function (LoF) mutations in one of three ge ... Full text Link to item Cite

Novel Neuroprotective Loci Modulating Ischemic Stroke Volume in Wild-Derived Inbred Mouse Strains.

Journal Article Genetics · November 2019 To identify genes involved in cerebral infarction, we have employed a forward genetic approach in inbred mouse strains, using quantitative trait loci (QTL) mapping for cerebral infarct volume after middle cerebral artery occlusion. We had previously observ ... Full text Open Access Link to item Cite

Circulating biomarkers associated with HHT phenotypes

Conference ANGIOGENESIS · November 1, 2019 Link to item Cite

Transcriptome clarifies mechanisms of lesion genesis versus progression in models of Ccm3 cerebral cavernous malformations.

Journal Article Acta Neuropathol Commun · August 19, 2019 Cerebral cavernous malformations (CCMs) are dilated capillaries causing epilepsy and stroke. Inheritance of a heterozygous mutation in CCM3/PDCD10 is responsible for the most aggressive familial form of the disease. Here we studied the differences and comm ... Full text Link to item Cite

ATTRACT.

Journal Article Circ Res · July 19, 2019 Full text Link to item Cite

Physical and Family History Variables Associated With Neurological and Cognitive Development in Sturge-Weber Syndrome.

Journal Article Pediatr Neurol · July 2019 BACKGROUND: Sturge-Weber syndrome (SWS) is caused by a somatic mutation in GNAQ leading to capillary venous malformations in the brain presenting with various neurological, ophthalmic, and cognitive symptoms of variable severity. This clinical variability ... Full text Link to item Cite

Biomarkers of cavernous angioma with symptomatic hemorrhage.

Journal Article JCI Insight · June 20, 2019 BACKGROUNDCerebral cavernous angiomas (CAs) with a symptomatic hemorrhage (CASH) have a high risk of recurrent hemorrhage and serious morbidity.METHODSEighteen plasma molecules with mechanistic roles in CA pathobiology were investigated in 114 patients and ... Full text Link to item Cite

Phenotypic characterization of murine models of cerebral cavernous malformations.

Journal Article Lab Invest · March 2019 Cerebral cavernous malformations (CCMs) are clusters of dilated capillaries that affect around 0.5% of the population. CCMs exist in two forms, sporadic and familial. Mutations in three documented genes, KRIT1(CCM1), CCM2, and PDCD10(CCM3), cause the autos ... Full text Link to item Cite

Rho Kinase Inhibition Blunts Lesion Development and Hemorrhage in Murine Models of Aggressive Pdcd10/Ccm3 Disease.

Journal Article Stroke · March 2019 Background and Purpose- Previously, murine models Krit1 +/- Msh2 -/- and Ccm2 +/- Trp53 -/- showed a reduction or no effect on cerebral cavernous malformation (CCM) burden and favorable effects on lesional hemorrhage by the robust Rock (Rho-associated prot ... Full text Link to item Cite

Comprehensive transcriptome analysis of cerebral cavernous malformation across multiple species and genotypes.

Journal Article JCI Insight · February 7, 2019 The purpose of this study was to determine important genes, functions, and networks contributing to the pathobiology of cerebral cavernous malformation (CCM) from transcriptomic analyses across 3 species and 2 disease genotypes. Sequencing of RNA from lase ... Full text Link to item Cite

Hereditary hemorrhagic telangiectasia (osler-weber-rendu syndrome)

Chapter · January 1, 2019 Hereditary hemorrhagic telangiectasia is an autosomal-dominant, highly penetrant, and variable multisystem disorder caused by maldevelopment of capillaries. The condition used to be called Osler-Weber-Rendu syndrome. The major features are epistaxis, mucoc ... Full text Cite

Cerebral Cavernous Malformations Develop Through Clonal Expansion of Mutant Endothelial Cells.

Journal Article Circ Res · October 26, 2018 RATIONALE: Vascular malformations arise in vessels throughout the entire body. Causative genetic mutations have been identified for many of these diseases; however, little is known about the mutant cell lineage within these malformations. OBJECTIVE: We uti ... Full text Link to item Cite

Neuronal IL-4Rα modulates neuronal apoptosis and cell viability during the acute phases of cerebral ischemia.

Journal Article FEBS J · August 2018 Ischemic stroke caused by an embolus or local thrombosis results in neural tissue damage (an infarct) in the territory of the occluded cerebral artery. Decades of studies have increased our understanding of the molecular events during cerebral infarction; ... Full text Open Access Link to item Cite

Association of common candidate variants with vascular malformations and intracranial hemorrhage in hereditary hemorrhagic telangiectasia.

Journal Article Mol Genet Genomic Med · May 2018 BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is caused by mutations in TGFβ/BMP9 pathway genes and characterized by vascular malformations (VM) including arteriovenous malformations (AVM) in lung, liver, and brain, which lead to severe complicat ... Full text Link to item Cite

Reliability and Clinical Correlation of Transcranial Doppler Ultrasound in Sturge-Weber Syndrome.

Journal Article Pediatr Neurol · September 2017 BACKGROUND: The reproducibility of transcranial Doppler (TCD) ultrasound measurements in Sturge-Weber syndrome (SWS) and TCD's ability to predict neurological progression is unknown. METHODS: In 14 individuals with SWS, TCD measured mean flow velocity, pul ... Full text Link to item Cite

BAG3 (Bcl-2-Associated Athanogene-3) Coding Variant in Mice Determines Susceptibility to Ischemic Limb Muscle Myopathy by Directing Autophagy.

Journal Article Circulation · July 18, 2017 BACKGROUND: Critical limb ischemia is a manifestation of peripheral artery disease that carries significant mortality and morbidity risk in humans, although its genetic determinants remain largely unknown. We previously discovered 2 overlapping quantitativ ... Full text Link to item Cite

RhoA Kinase Inhibition With Fasudil Versus Simvastatin in Murine Models of Cerebral Cavernous Malformations.

Journal Article Stroke · January 2017 BACKGROUND AND PURPOSE: We sought to compare the effect of chronic treatment with commonly tolerated doses of Fasudil, a specific RhoA kinase (ROCK) inhibitor, and simvastatin (with pleiotropic effects including ROCK inhibition) on cerebral cavernous malfo ... Full text Link to item Cite

The pathobiology of vascular malformations: insights from human and model organism genetics.

Journal Article J Pathol · January 2017 Vascular malformations may arise in any of the vascular beds present in the human body. These lesions vary in location, type, and clinical severity of the phenotype. In recent years, the genetic basis of several vascular malformations has been elucidated. ... Full text Link to item Cite

Micro-computed tomography in murine models of cerebral cavernous malformations as a paradigm for brain disease.

Journal Article J Neurosci Methods · September 15, 2016 BACKGROUND: Cerebral cavernous malformations (CCMs) are hemorrhagic brain lesions, where murine models allow major mechanistic discoveries, ushering genetic manipulations and preclinical assessment of therapies. Histology for lesion counting and morphometr ... Full text Link to item Cite

Natural allelic variation of the IL-21 receptor modulates ischemic stroke infarct volume.

Journal Article J Clin Invest · August 1, 2016 Risk for ischemic stroke has a strong genetic basis, but heritable factors also contribute to the extent of damage after a stroke has occurred. We previously identified a locus on distal mouse chromosome 7 that contributes over 50% of the variation in post ... Full text Open Access Link to item Cite

B-Cell Depletion Reduces the Maturation of Cerebral Cavernous Malformations in Murine Models.

Journal Article J Neuroimmune Pharmacol · June 2016 Cerebral cavernous malformations (CCMs) are relatively common vascular malformations, characterized by increased Rho kinase (ROCK) activity, vascular hyper-permeability and the presence of blood degradation products including non-heme iron. Previous studie ... Full text Link to item Cite

Leveraging a Sturge-Weber Gene Discovery: An Agenda for Future Research.

Journal Article Pediatr Neurol · May 2016 Sturge-Weber syndrome (SWS) is a vascular neurocutaneous disorder that results from a somatic mosaic mutation in GNAQ, which is also responsible for isolated port-wine birthmarks. Infants with SWS are born with a cutaneous capillary malformation (port-wine ... Full text Link to item Cite

ADAM12: a genetic modifier of preclinical peripheral arterial disease.

Journal Article Am J Physiol Heart Circ Physiol · September 2015 In prior studies from multiple groups, outcomes following experimental peripheral arterial disease (PAD) differed considerably across inbred mouse strains. Similarly, in humans with PAD, disease outcomes differ, even when there are similarities in risk fac ... Full text Link to item Cite

Exceptional aggressiveness of cerebral cavernous malformation disease associated with PDCD10 mutations.

Journal Article Genet Med · March 2015 PURPOSE: The phenotypic manifestations of cerebral cavernous malformation disease caused by rare PDCD10 mutations have not been systematically examined, and a mechanistic link to Rho kinase-mediated hyperpermeability, a potential therapeutic target, has no ... Full text Link to item Cite

Sturge-Weber Syndrome

Chapter · November 13, 2014 Sturge-Weber syndrome (SWS) is the association of the facial port-wine birthmark with malformed leptomeningeal blood vessels and abnormal venous eye vessels. Occurrence is sporadic and in both males and females and reported in all racial and ethnic backgro ... Full text Cite

Lesions from patients with sporadic cerebral cavernous malformations harbor somatic mutations in the CCM genes: evidence for a common biochemical pathway for CCM pathogenesis.

Journal Article Hum Mol Genet · August 15, 2014 Cerebral cavernous malformations (CCMs) are vascular lesions affecting the central nervous system. CCM occurs either sporadically or in an inherited, autosomal dominant manner. Constitutional (germline) mutations in any of three genes, KRIT1, CCM2 and PDCD ... Full text Link to item Cite

Endoglin deficiency impairs stroke recovery.

Journal Article Stroke · July 2014 BACKGROUND AND PURPOSE: Endoglin deficiency causes hereditary hemorrhagic telangiectasia-1 and impairs myocardial repair. Pulmonary arteriovenous malformations in patients with hereditary hemorrhagic telangiectasia-1 are associated with a high incidence of ... Full text Link to item Cite

Inhibition of the cardiomyocyte-specific troponin I-interacting kinase limits oxidative stress, injury, and adverse remodeling due to ischemic heart disease.

Journal Article Circ Res · March 14, 2014 Ischemia–reperfusion injury is strongly associated with increased oxidative stress, mitochondrial dysfunction, and cell death. These processes are diminished in an animal model of ischemia–reperfusion by the genetic loss or pharmacological inhibition of tr ... Full text Link to item Cite

EndoU is a novel regulator of AICD during peripheral B cell selection.

Journal Article J Exp Med · January 13, 2014 Balanced transmembrane signals maintain a competent peripheral B cell pool limited in self-reactive B cells that may produce pathogenic autoantibodies. To identify molecules regulating peripheral B cell survival and tolerance to self-antigens (Ags), a gene ... Full text Link to item Cite

A novel genetic locus modulates infarct volume independently of the extent of collateral circulation.

Journal Article Physiol Genomics · September 3, 2013 In the mouse model of permanent, middle cerebral artery occlusion, infarct volume varies widely across inbred strains but generally is inversely correlated with collateral vessel number. However, we also observed certain mouse strains that share similar co ... Full text Link to item Cite

Sturge-Weber syndrome and port-wine stains caused by somatic mutation in GNAQ.

Journal Article N Engl J Med · May 23, 2013 BACKGROUND: The Sturge-Weber syndrome is a sporadic congenital neurocutaneous disorder characterized by a port-wine stain affecting the skin in the distribution of the ophthalmic branch of the trigeminal nerve, abnormal capillary venous vessels in the lept ... Full text Link to item Cite

Brain Vascular Malformation Consortium: Overview, Progress and Future Directions.

Journal Article J Rare Disord · April 1, 2013 Brain vascular malformations are resource-intensive to manage effectively, are associated with serious neurological morbidity, lack specific medical therapies, and have no validated biomarkers for disease severity and progression. Investigators have tended ... Link to item Cite

Overexpression of TNNI3K, a cardiac-specific MAPKKK, promotes cardiac dysfunction.

Journal Article J Mol Cell Cardiol · January 2013 Cardiac troponin I-interacting kinase (TNNI3K) is a cardiac-specific kinase whose biological function remains largely unknown. We have recently shown that TNNI3K expression greatly accelerates cardiac dysfunction in mouse models of cardiomyopathy, indicati ... Full text Link to item Cite

Natural genetic variation of integrin alpha L (Itgal) modulates ischemic brain injury in stroke.

Journal Article PLoS Genet · 2013 During ischemic stroke, occlusion of the cerebrovasculature causes neuronal cell death (infarction), but naturally occurring genetic factors modulating infarction have been difficult to identify in human populations. In a surgically induced mouse model of ... Full text Open Access Link to item Cite

Skeletal muscle-specific genetic determinants contribute to the differential strain-dependent effects of hindlimb ischemia in mice.

Journal Article Am J Pathol · May 2012 Genetics plays an important role in determining peripheral arterial disease (PAD) pathology, which causes a spectrum of clinical disorders that range from clinically silent reductions in blood flow to limb-threatening ischemia. The cell-type specificity of ... Full text Link to item Cite

Updates and future horizons on the understanding, diagnosis, and treatment of Sturge-Weber syndrome brain involvement.

Journal Article Dev Med Child Neurol · March 2012 AIM: To review recent developments in the understanding, diagnosis, and treatment of Sturge-Weber syndrome (SWS). METHOD: Members of the Brain Vascular Malformation Consortium Sturge-Weber Syndrome National Workgroup contributed their expertise to review t ... Full text Link to item Cite

Fasudil decreases lesion burden in a murine model of cerebral cavernous malformation disease.

Journal Article Stroke · February 2012 BACKGROUND AND PURPOSE: Cerebral cavernous malformations (CCMs) are characterized by grossly dilated capillaries, associated with vascular leak and hemorrhage, and occur in sporadic or inherited (autosomal-dominant) forms with mutations in 1 of 3 gene loci ... Full text Link to item Cite

Dissection of a quantitative trait locus for PR interval duration identifies Tnni3k as a novel modulator of cardiac conduction.

Journal Article PLoS Genet · 2012 Atrio-ventricular conduction disease is a common feature in Mendelian rhythm disorders associated with sudden cardiac death and is characterized by prolongation of the PR interval on the surface electrocardiogram (ECG). Prolongation of the PR interval is a ... Full text Link to item Cite

A founder mutation in the Ashkenazi Jewish population affecting messenger RNA splicing of the CCM2 gene causes cerebral cavernous malformations.

Journal Article Genet Med · July 2011 PURPOSE: Cerebral cavernous malformations can occur sporadically or are caused by mutations in one of three identified genes. Cerebral cavernous malformations often remain clinically silent until a mutation carrier suffers a stroke or seizure. Presymptomat ... Full text Link to item Cite

A novel mouse model of cerebral cavernous malformations based on the two-hit mutation hypothesis recapitulates the human disease.

Journal Article Hum Mol Genet · January 15, 2011 Cerebral cavernous malformations (CCMs) are vascular lesions of the central nervous system appearing as multicavernous, blood-filled capillaries, leading to headache, seizure and hemorrhagic stroke. CCM occurs either sporadically or as an autosomal dominan ... Full text Link to item Cite

Two genes on A/J chromosome 18 are associated with susceptibility to Staphylococcus aureus infection by combined microarray and QTL analyses.

Journal Article PLoS Pathog · September 2, 2010 Although it has recently been shown that A/J mice are highly susceptible to Staphylococcus aureus sepsis as compared to C57BL/6J, the specific genes responsible for this differential phenotype are unknown. Using chromosome substitution strains (CSS), we fo ... Full text Open Access Link to item Cite

Functional conservation of human Spastin in a Drosophila model of autosomal dominant-hereditary spastic paraplegia.

Journal Article Hum Mol Genet · May 15, 2010 Mutations in spastin are the most frequent cause of the neurodegenerative disease autosomal dominant-hereditary spastic paraplegia (AD-HSP). Drosophila melanogaster lacking spastin exhibit striking behavioral similarities to human patients suffering from A ... Full text Link to item Cite

Overlapping spectra of SMAD4 mutations in juvenile polyposis (JP) and JP-HHT syndrome.

Journal Article Am J Med Genet A · February 2010 Juvenile polyposis (JP) and hereditary hemorrhagic telangiectasia (HHT) are clinically distinct diseases caused by mutations in SMAD4 and BMPR1A (for JP) and endoglin and ALK1 (for HHT). Recently, a combined syndrome of JP-HHT was described that is also ca ... Full text Link to item Cite

A locus mapping to mouse chromosome 7 determines infarct volume in a mouse model of ischemic stroke.

Journal Article Circ Cardiovasc Genet · December 2009 BACKGROUND: In a mouse model of focal cerebral ischemia, infarct volume is highly variable and strain dependent, but the natural genetic determinants responsible for this difference remain unknown. To identify genetic determinants regulating ischemic neuro ... Full text Link to item Cite

Tnni3k modifies disease progression in murine models of cardiomyopathy.

Journal Article PLoS Genet · September 2009 The Calsequestrin (Csq) transgenic mouse model of cardiomyopathy exhibits wide variation in phenotypic progression dependent on genetic background. Seven heart failure modifier (Hrtfm) loci modify disease progression and outcome. Here we report Tnni3k (car ... Full text Link to item Cite

An N-ethyl-N-nitrosourea mutagenesis recessive screen identifies two candidate regions for murine cardiomyopathy that map to chromosomes 1 and 15.

Journal Article Mamm Genome · May 2009 N-ethyl-N-nitrosourea (ENU) mutagenesis screens have been successful for identifying genes that affect important biological processes and diseases. However, for heart-related phenotypes, these screens have been employed exclusively for developmental phenot ... Full text Link to item Cite

Biallelic somatic and germline mutations in cerebral cavernous malformations (CCMs): evidence for a two-hit mechanism of CCM pathogenesis.

Journal Article Hum Mol Genet · March 1, 2009 Cerebral cavernous malformations (CCMs) are vascular anomalies of the central nervous system, comprising dilated blood-filled capillaries lacking structural support. The lesions are prone to rupture, resulting in seizures or hemorrhagic stroke. CCM can occ ... Full text Link to item Cite

The cerebral cavernous malformation signaling pathway promotes vascular integrity via Rho GTPases.

Journal Article Nat Med · February 2009 Cerebral cavernous malformation (CCM) is a common vascular dysplasia that affects both systemic and central nervous system blood vessels. Loss of function mutations in the CCM2 gene cause CCM. Here we show that targeted disruption of Ccm2 in mice results i ... Full text Link to item Cite

Increased tissue perfusion promotes capillary dysplasia in the ALK1-deficient mouse brain following VEGF stimulation.

Journal Article Am J Physiol Heart Circ Physiol · December 2008 Loss-of-function activin receptor-like kinase 1 gene mutation (ALK1+/-) is associated with brain arteriovenous malformations (AVM) in hereditary hemorrhagic telangiectasia type 2. Other determinants of the lesional phenotype are unknown. In the present stu ... Full text Link to item Cite

Advanced magnetic resonance imaging of cerebral cavernous malformations: part II. Imaging of lesions in murine models.

Journal Article Neurosurgery · October 2008 OBJECTIVE: We sought to assess the appearance of cerebral cavernous malformations (CCM) on magnetic resonance imaging (MRI) scans in murine Ccm1 and Ccm2 gene knockout models and to develop a technique of lesion localization for correlative pathobiological ... Full text Link to item Cite

ZPLD1 gene is disrupted in a patient with balanced translocation that exhibits cerebral cavernous malformations.

Journal Article Neuroscience · August 13, 2008 The past few years have seen rapid advances in our understanding of the genetics and molecular biology of cerebral cavernous malformations (CCM) with the identification of the CCM1, CCM2, and CCM3 genes. Recently, we have recruited a patient with an X/3 ba ... Full text Link to item Cite

A quantitative trait locus (LSq-1) on mouse chromosome 7 is linked to the absence of tissue loss after surgical hindlimb ischemia.

Journal Article Circulation · March 4, 2008 BACKGROUND: Peripheral arterial disease (PAD) caused by occlusive atherosclerosis of the lower extremity has 2 major clinical manifestations. Critical limb ischemia is characterized by rest pain and/or tissue loss and has a > or = 40% risk of death and maj ... Full text Link to item Cite

Different spectra of genomic deletions within the CCM genes between Italian and American CCM patient cohorts.

Journal Article Neurogenetics · February 2008 Cerebral cavernous malformations (CCMs) are vascular abnormalities of the brain that can result in hemorrhagic stroke and seizures. Familial forms of CCM are inherited in an autosomal-dominant fashion, and three CCM genes have been identified. We recently ... Full text Link to item Cite

Childhood socioeconomic status and serotonin transporter gene polymorphism enhance cardiovascular reactivity to mental stress.

Journal Article Psychosom Med · January 2008 OBJECTIVE: To test the hypothesis that low socioeconomic status (SES) and the 5HTTLPR L allele are associated with increased cardiovascular reactivity (CVR) to stress in a larger sample and that SES and 5HTTLPR genotypes interact to enhance CVR to stress. ... Full text Link to item Cite

Genetic considerations relevant to intracranial hemorrhage and brain arteriovenous malformations.

Journal Article Acta Neurochir Suppl · 2008 Brain arteriovenous malformations (AVMs) cause intracranial hemorrhage (ICH), especially in young adults. Molecular characterization of lesional tissue provides evidence for involvement of both angiogenic and inflammatory pathways, but the pathogenesis rem ... Full text Link to item Cite

Neonatal co-infection with helicobacter species markedly accelerates the development of inflammation-associated colonic neoplasia in IL-10(-/-) mice.

Journal Article Helicobacter · December 2007 BACKGROUND: Inflammatory bowel disease (IBD) is hypothesized to represent an aberrant immune response against enteric bacteria that occurs in a genetically susceptible host. Humans and mice with IBD are at markedly increased risk for colonic neoplasia. How ... Full text Link to item Cite

Hypertension and albuminuria in chronic kidney disease mapped to a mouse chromosome 11 locus.

Journal Article Kidney Int · November 2007 Chronic kidney disease (CKD) is a key cause of hypertension and a potent independent risk for cardiovascular disease. Epidemiological studies suggest a strong genetic component determining susceptibility for renal disease and, by inference, the associated ... Full text Link to item Cite

Genetic analysis of a family with hereditary glomuvenous malformations.

Journal Article Australas J Dermatol · August 2007 Glomuvenous malformations (MIM 138000) are rare vascular malformations consisting of glomus cells, and in affected individuals, lesions may appear in any number anywhere on the body. We analysed the DNA of one family with hereditary glomuvenous malformatio ... Full text Link to item Cite

Highly variable penetrance in subjects affected with cavernous cerebral angiomas (CCM) carrying novel CCM1 and CCM2 mutations.

Journal Article Am J Med Genet B Neuropsychiatr Genet · July 5, 2007 Cavernous vascular malformations may affect brain and out-of-brain tissues. In most cases, cerebral cavernous malformations (CCMs) involve the brain alone, and are rarely associated with skin hemangiomas, spinal cord, retinal, hepatic or vertebral lesions. ... Full text Link to item Cite

Arteriovenous malformation.

Journal Article J Neurosurg · April 2007 Full text Link to item Cite

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Journal Article Journal of the American College of Cardiology · March 13, 2007 Full text Cite

Deletions in CCM2 are a common cause of cerebral cavernous malformations.

Journal Article Am J Hum Genet · January 2007 Cerebral cavernous malformations (CCMs) are vascular abnormalities of the brain that can result in a variety of neurological disabilities, including hemorrhagic stroke and seizures. Mutations in the gene KRIT1 are responsible for CCM1, mutations in the gen ... Full text Link to item Cite

No evidence for maternal-fetal microchimerism in infantile hemangioma: a molecular genetic investigation.

Journal Article J Invest Dermatol · November 2006 In this study, using the placental origin theory as a basis, we set out to explore whether hemangioma endothelial cells (HEC) were maternal in origin. We rigorously addressed this hypothesis using several molecular genetic techniques. Fluorescent in situ h ... Full text Link to item Cite

Redefining heart failure: the utility of genomics.

Journal Article J Am Coll Cardiol · October 3, 2006 In this era of genomics, new technologies and the information that they generate have a wide range of potential applications to heart failure. Though there has not been widespread practical use of genomic information in everyday practice, there are many ex ... Full text Link to item Cite

SMAD4 mutations found in unselected HHT patients.

Journal Article J Med Genet · October 2006 BACKGROUND: Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant disease exhibiting multifocal vascular telangiectases and arteriovenous malformations. The majority of cases are caused by mutations in either the endoglin (ENG) or activin r ... Full text Link to item Cite

Precocious osteoarthritis in a family with recurrent COL2A1 mutation.

Journal Article J Rheumatol · June 2006 OBJECTIVE: To examine the genotypic and phenotypic characteristics of a Micronesian kindred with autosomal dominant precocious osteoarthritis (OA). METHODS: We reviewed records and radiographs of 3 index patients and their parents, administered questionnai ... Link to item Cite

ALK1 signalling analysis identifies angiogenesis related genes and reveals disparity between TGF-beta and constitutively active receptor induced gene expression.

Journal Article BMC Cardiovasc Disord · April 4, 2006 BACKGROUND: TGF-beta1 is an important angiogenic factor involved in the different aspects of angiogenesis and vessel maintenance. TGF-beta signalling is mediated by the TbetaRII/ALK5 receptor complex activating the Smad2/Smad3 pathway. In endothelial cells ... Full text Link to item Cite

Genomic characterization of POS5, the Saccharomyces cerevisiae mitochondrial NADH kinase.

Journal Article Mitochondrion · April 2006 Disruption of the Saccharomyces cerevisiae mitochondrial NADH kinase POS5 increases the mitochondrial mutation rate 50-fold. Whereas most multicellular eukaryotic genomes have one NADH kinase gene, the yeast genome contains three distinct genes encoding NA ... Full text Link to item Cite

Genomic characterization of POS5, the Saccharomyces cerevisiae mitochondrial NADH kinase.

Journal Article Mitochondrion. · April 1, 2006 Disruption of the Saccharomyces cerevisiae mitochondrial NADH kinase POS5 increases the mitochondrial mutation rate 50-fold. Whereas most multicellular eukaryotic genomes have one NADH kinase gene, the yeast genome contains three distinct genes encoding NA ... Cite

Neuronal expression of the Ccm2 gene in a new mouse model of cerebral cavernous malformations.

Journal Article Mamm Genome · February 2006 Cerebral cavernous malformations are vascular defects of the central nervous system consisting of clusters of dilated vessels that are subject to frequent hemorrhaging. The genes mutated in three forms of autosomal dominant cerebral cavernous malformations ... Full text Link to item Cite

Low frequency of PDCD10 mutations in a panel of CCM3 probands: potential for a fourth CCM locus.

Journal Article Hum Mutat · January 2006 Cerebral cavernous malformations (CCMs) are vascular abnormalities of the brain that can result in a variety of neurological disabilities, including stroke and seizures. Linkage analyses using autosomal dominant families manifesting CCMs have identified th ... Full text Link to item Cite

Tumor necrosis factor-alpha-238G>A promoter polymorphism is associated with increased risk of new hemorrhage in the natural course of patients with brain arteriovenous malformations.

Journal Article Stroke · January 2006 BACKGROUND AND PURPOSE: Identification of single-nucleotide polymorphisms (SNPs) associated with increased risk of new intracranial hemorrhage (ICH) after brain arteriovenous malformation (BAVM) diagnosis would facilitate risk stratification and identify p ... Full text Link to item Cite

Molecular classification of patients with unexplained hamartomatous and hyperplastic polyposis.

Journal Article JAMA · November 16, 2005 CONTEXT: Significant proportions of patients with hamartomatous polyposis or with hyperplastic/mixed polyposis remain without specific clinical and molecular diagnosis or present atypically. Assigning a syndromic diagnosis is important because it guides ma ... Full text Link to item Cite

Polymorphisms in transforming growth factor-beta-related genes ALK1 and ENG are associated with sporadic brain arteriovenous malformations.

Journal Article Stroke · October 2005 BACKGROUND AND PURPOSE: Mutations in endoglin (ENG) and activin-like kinase (ALK1) cause hereditary hemorrhagic telangiectasias, disorders characterized by pulmonary and brain arteriovenous malformations (BAVMs). We investigated whether polymorphisms in th ... Full text Link to item Cite

Subcellular localization of spastin: implications for the pathogenesis of hereditary spastic paraplegia.

Journal Article Neurogenetics · September 2005 Hereditary spastic paraplegia (HSP) is a group of clinically and genetically heterogeneous diseases characterized by neuronal degeneration that is maximal at the distal ends of the longest axons of the central nervous system. The most common cause of autos ... Full text Link to item Cite

Genetics of cerebral cavernous malformations.

Journal Article Curr Neurol Neurosci Rep · September 2005 The past few years have seen rapid advances in our understanding of the genetics and molecular biology of cerebral cavernous malformations (CCM). This article summarizes the recent cloning of the CCM1, CCM2, and CCM3 genes, which are responsible for autoso ... Full text Link to item Cite

CCM1 and CCM2 protein interactions in cell signaling: implications for cerebral cavernous malformations pathogenesis.

Journal Article Hum Mol Genet · September 1, 2005 Cerebral cavernous malformations (CCMs) are sporadically acquired or inherited vascular lesions of the central nervous system consisting of clusters of dilated thin-walled blood vessels that predispose individuals to seizures and stroke. Familial CCM is ca ... Full text Link to item Cite

QTL mapping in a mouse model of cardiomyopathy reveals an ancestral modifier allele affecting heart function and survival.

Journal Article Mamm Genome · June 2005 The progression from myocardial hypertrophy to heart failure is a complex process, involving genetic and environmental factors. Elucidating the genetic components contributing to heart failure has been difficult, largely because of the heterogeneity of hum ... Full text Link to item Cite

Influence of serotonin transporter promoter region polymorphisms on hippocampal volumes in late-life depression.

Journal Article Arch Gen Psychiatry · May 2005 CONTEXT: Polymorphisms in the promoter region of the serotonin transporter gene (5-HTTLPR) influence transcription and may play a role in the pathogenesis and course of depression. Recent research demonstrates that specific polymorphisms may be associated ... Full text Link to item Cite

Human retroviral gag- and gag-pol-like proteins interact with the transforming growth factor-beta receptor activin receptor-like kinase 1.

Journal Article J Biol Chem · March 4, 2005 Mutations in activin receptor-like kinase 1 (ALK1), a transforming growth factor (TGF)-beta type I receptor, lead to the vascular disorder hereditary hemorrhagic telangiectasia caused by abnormal vascular remodeling. The underlying molecular cause of this ... Full text Link to item Cite

Functional analysis of a mutant form of the receptor tyrosine kinase Tie2 causing venous malformations.

Journal Article J Mol Med (Berl) · January 2005 Tie2 is expressed predominantly in endothelial cells and is required for blood vessel formation and maintenance. A missense mutation resulting in an R to W substitution in the kinase domain of Tie2 co-segregates with an autosomal dominantly inherited form ... Full text Link to item Cite

Loss of p53 sensitizes mice with a mutation in Ccm1 (KRIT1) to development of cerebral vascular malformations.

Journal Article Am J Pathol · November 2004 Cerebral cavernous malformations (CCM) consist of clusters of abnormally dilated blood vessels. Hemorrhaging of these lesions can cause seizures and lethal stroke. Three loci are associated with autosomal dominant CCM, and the causative genes have been ide ... Full text Link to item Cite

Polymorphisms in genes involved in inflammatory and angiogenic pathways and the risk of hemorrhagic presentation of brain arteriovenous malformations.

Journal Article Stroke · October 2004 BACKGROUND AND PURPOSE: Accurate estimates of intracranial hemorrhage (ICH) risk in patients harboring brain arteriovenous malformation (BAVM) are needed to evaluate interventional strategies and to help guide clinical management. Identification of genetic ... Full text Link to item Cite

Giant infiltrative cavernous malformation: clinical presentation, intervention, and genetic analysis: case report.

Journal Article Neurosurgery · October 2004 OBJECTIVE AND IMPORTANCE: Cavernous malformations can present in children with a sporadic course of repeated hemorrhage and enlargement, but they are rarely aggressive, infiltrative, or multilobar. We present the case of a young boy with a complex cavernou ... Full text Link to item Cite

Intragenic modifiers of hereditary spastic paraplegia due to spastin gene mutations.

Journal Article Neurogenetics · September 2004 Hereditary spastic paraplegia (HSP) is a genetically heterogeneous neurodegenerative disease characterized by wide variability in phenotypic expression, both within and among families. The most-common cause of autosomal dominant HSP is mutation of the gene ... Full text Link to item Cite

A combined syndrome of juvenile polyposis and hereditary haemorrhagic telangiectasia associated with mutations in MADH4 (SMAD4).

Journal Article Lancet · March 13, 2004 BACKGROUND: Juvenile polyposis and hereditary haemorrhagic telangiectasia are autosomal dominant disorders with distinct and non-overlapping clinical features. The former, an inherited gastrointestinal malignancy predisposition, is caused by mutations in M ... Full text Link to item Cite

Primary pulmonary hypertension in families with hereditary haemorrhagic telangiectasia.

Journal Article Eur Respir J · March 2004 Primary pulmonary hypertension (PPH) is a rare but severe and progressive disease characterised by obstructive lesions of small pulmonary arteries. Patients with PPH often have mutations in the bone morphogenetic protein receptor type II (BMPR2) gene, wher ... Full text Link to item Cite

Ccm1 is required for arterial morphogenesis: implications for the etiology of human cavernous malformations.

Journal Article Development · March 2004 Hemorrhagic stroke is a significant cause of morbidity and mortality in children, and is frequently associated with intracranial vascular malformations. One prevalent form of these vascular malformations, cerebral cavernous malformation, is characterized b ... Full text Link to item Cite

Modifier locus on mouse chromosome 3 for renal vascular pathology in AT1A receptor-deficiency.

Journal Article Hypertension · February 2004 We previously showed that the phenotype of mice with targeted disruption of the gene encoding the AT1A receptor (Agtr1a), the major murine AT1 receptor isoform, is strongly influenced by recessive genetic modifiers derived from the C57BL/6 or 129 inbred st ... Full text Link to item Cite

Gene microarray analysis of human brain arteriovenous malformations.

Journal Article Neurosurgery · February 2004 OBJECTIVE: Human brain arteriovenous malformations (BAVMs) display abnormal expression of various angiogenesis-related genes and their products. We examined gene expression patterns in BAVMs by the gene microarray technique. METHODS: We analyzed BAVM and c ... Full text Link to item Cite

Vascular endothelial growth factor induces abnormal microvasculature in the endoglin heterozygous mouse brain.

Journal Article J Cereb Blood Flow Metab · February 2004 Hereditary hemorrhagic telangiectasia (HHT), associated with brain arteriovenous malformations, is caused by a loss of function mutation in either the endoglin (HHT1) or activin receptor-like kinase 1 gene (ALK-1, HHT2). Endoglin heterozygous (Eng+/-)mice ... Full text Link to item Cite

Multiple quantitative trait loci modify the heart failure phenotype in murine cardiomyopathy.

Journal Article Hum Mol Genet · December 1, 2003 The variability in outcome of heart failure patients depends on a number of factors including differences in their genetic background. To identify novel genes that modify the human heart failure phenotype, we used a strategy of quantitative trait locus (QT ... Full text Link to item Cite

Mutations in a gene encoding a novel protein containing a phosphotyrosine-binding domain cause type 2 cerebral cavernous malformations.

Journal Article Am J Hum Genet · December 2003 Cerebral cavernous malformations (CCMs) are congenital vascular anomalies of the central nervous system that can result in hemorrhagic stroke, seizures, recurrent headaches, and focal neurologic deficits. Mutations in the gene KRIT1 are responsible for typ ... Full text Link to item Cite

Molecular analysis of the glomulin gene in glomuvenous malformation families

Conference AMERICAN JOURNAL OF HUMAN GENETICS · November 1, 2003 Link to item Cite

A Genomic screen reveals evidence for novel SPG loci.

Conference AMERICAN JOURNAL OF HUMAN GENETICS · November 1, 2003 Link to item Cite

Hereditary haemorrhagic telangiectasia: a questionnaire based study to delineate the different phenotypes caused by endoglin and ALK1 mutations.

Journal Article J Med Genet · August 2003 BACKGROUND: Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant vascular dysplasia characterised by mucocutaneous telangiectasis, epistaxis, gastrointestinal haemorrhage, and arteriovenous malformations in the lung and brain. Causative mu ... Full text Link to item Cite

Vascular morphogenesis: tales of two syndromes.

Journal Article Hum Mol Genet · April 1, 2003 Featured Publication Advances in our understanding of fundamental biological processes can be made by the analysis of defects manifested in inherited diseases. The genes responsible for these genetic syndromes often encode proteins that act at critical points of the pathways t ... Full text Link to item Cite

Impact of genetic polymorphisms on heart failure prognosis.

Journal Article Arch Mal Coeur Vaiss · March 2003 Featured Publication Recent progress in genomic applications have led to a better understanding of the relationship between genetic background and cardiovascular diseases such as heart failure. The broad variability in heart failure patient outcome is in part secondary to modi ... Link to item Cite

A mouse model for hereditary hemorrhagic telangiectasia (HHT) type 2.

Journal Article Hum Mol Genet · March 1, 2003 Featured Publication Hereditary hemorrhagic telangiectasia (HHT) is an autosomal-dominant disorder characterized by the age-dependent development of focal arteriovenous malformations and telangiectases. HHT type 2 is caused by loss of function mutations in activin receptor-lik ... Full text Link to item Cite

Serotonin-related gene polymorphisms and central nervous system serotonin function.

Journal Article Neuropsychopharmacology · March 2003 Central nervous system (CNS) serotonergic function affects a wide range of biological and behavioral functions affecting health and disease. Our objective in this study was to determine whether functional polymorphisms of the genes that encode for the sero ... Full text Link to item Cite

Associations among the NEO Personality Inventory, Revised and the serotonin transporter gene-linked polymorphic region in elders: effects of depression and gender.

Journal Article Psychiatr Genet · March 2003 OBJECTIVE: The short variant of the serotonin transporter gene-linked functional polymorphic region (5-HTTLPR) has been associated with personality traits related to anxiety, hostility, and depression. We attempted to replicate findings suggesting a positi ... Full text Link to item Cite

A kinesin heavy chain (KIF5A) mutation in hereditary spastic paraplegia (SPG10).

Journal Article Am J Hum Genet · November 2002 Featured Publication We have identified a missense mutation in the motor domain of the neuronal kinesin heavy chain gene KIF5A, in a family with hereditary spastic paraplegia. The mutation occurs in the family in which the SPG10 locus was originally identified, at an invariant ... Full text Link to item Cite

A murine model for hereditary hemorrhagic telangiectasia type 2.

Conference AMERICAN JOURNAL OF HUMAN GENETICS · October 1, 2002 Link to item Cite

A kinesin heavy chain (KIF5A) mutation in Hereditary Spastic Paraplegia (SPG10).

Conference AMERICAN JOURNAL OF HUMAN GENETICS · October 1, 2002 Link to item Cite

Genetic modifier loci affecting survival and cardiac function in murine dilated cardiomyopathy.

Journal Article Circulation · April 16, 2002 Featured Publication BACKGROUND: Understanding the role for genetic factors in human heart failure is difficult because environmental factors cannot be standardized and genetic variation is great. One approach to identify genes that modify disease outcome is to use mouse model ... Full text Link to item Cite

Somatic mutation of vascular endothelial growth factor receptors in juvenile hemangioma.

Journal Article Genes Chromosomes Cancer · March 2002 Featured Publication Juvenile hemangiomas are the most common tumors of infancy, occurring in as many as 10% of all births. These benign vascular lesions enlarge rapidly during the first year of life by hyperplasia of endothelial cells and attendant pericytes and then spontane ... Full text Link to item Cite

KRIT1 association with the integrin-binding protein ICAP-1: a new direction in the elucidation of cerebral cavernous malformations (CCM1) pathogenesis.

Journal Article Hum Mol Genet · February 15, 2002 Featured Publication Mutations in KRIT1, a protein initially identified based on a yeast two-hybrid interaction with the RAS-family GTPase RAP1A, are responsible for the development of the inherited vascular disorder cerebral cavernous malformations (CCM1). As the function of ... Full text Link to item Cite

Allelic differences in the serotonin transporter-linked polymorphic region in geriatric depression.

Journal Article Am J Geriatr Psychiatry · 2002 Previous studies have examined the role of genetic variations in the serotonin transporter-linked polymorphic region (5HTTLPR) in affective disorders. The authors studied 182 older depressed subjects and 107 elderly control subjects and obtained DNA for ge ... Link to item Cite

The CCM1 gene product KRIT1 interacts with the integrin binding protein ICAP-1.

Conference AMERICAN JOURNAL OF HUMAN GENETICS · October 1, 2001 Link to item Cite

Somatic mutations in sporadic juvenile hemangioma.

Conference AMERICAN JOURNAL OF HUMAN GENETICS · October 1, 2001 Link to item Cite

Identification and expression analysis of spastin gene mutations in hereditary spastic paraplegia.

Journal Article Am J Hum Genet · May 2001 Pure hereditary spastic paraplegia (SPG) type 4 is the most common form of autosomal dominant hereditary SPG, a neurodegenerative disease characterized primarily by hyperreflexia and progressive spasticity of the lower limbs. It is caused by mutations in t ... Full text Link to item Cite

Pathogenesis of hemangioma.

Journal Article J Clin Invest · March 2001 Featured Publication Full text Link to item Cite

Evidence for loss of heterozygosity of 5q in sporadic haemangiomas: are somatic mutations involved in haemangioma formation?

Journal Article J Clin Pathol · March 2001 Featured Publication BACKGROUND/AIMS: Haemangiomas are common benign tumours of infancy that consist of rapidly proliferating endothelial cells. A locus for an autosomal dominant predisposition to haemangioma has been identified recently on chromosome 5q. This study aimed to i ... Full text Link to item Cite

Fine mapping and genetic heterogeneity in the pure form of autosomal dominant familial spastic paraplegia.

Journal Article Neurogenetics · March 2001 We evaluated seven families segregating pure, autosomal dominant familial spastic paraplegia (SPG) for linkage to four recently identified SPG loci on chromosomes 2q (1), 8q (2), 12q (3), and 19q (4). These families were previously shown to be unlinked to ... Full text Link to item Cite

Central nervous system serotonin function and cardiovascular responses to stress.

Journal Article Psychosom Med · 2001 Featured Publication OBJECTIVE: The objective of this study was to evaluate the impact of indices of central nervous system (CNS) serotonin function on cardiovascular reactivity to mental stress. METHODS: Lumbar puncture was performed on 54 healthy volunteers to obtain cerebro ... Full text Link to item Cite

Additional glomangioma families link to chromosome 1p: no evidence for genetic heterogeneity.

Journal Article Hum Hered · 2001 Venous malformations are a common abnormality of the vasculature that may occur sporadically or, more rarely, as an autosomal dominant trait. One familial form of venous malformations has previously been linked to chromosome 9p. Mutations in the gene encod ... Full text Link to item Cite

Computational and experimental analyses reveal previously undetected coding exons of the KRIT1 (CCM1) gene.

Journal Article Genomics · January 1, 2001 A notable difficulty in annotating genomic sequence is identifying the correct start codon in a gene. An important such case has been found with KRIT1, the cerebral cavernous malformation type 1 (CCM1) gene. Analysis of human and mouse genomic sequence enc ... Full text Link to item Cite

Abnormal pattern of Tie-2 and vascular endothelial growth factor receptor expression in human cerebral arteriovenous malformations.

Journal Article Neurosurgery · October 2000 OBJECTIVE: Human cerebral arteriovenous malformations (AVMs) are speculated to result from abnormal angiogenesis. Vascular endothelial growth factor receptors (VEGF-Rs) and Tie-2 play critical roles in vasculogenesis and angiogenesis. We hypothesized that ... Full text Link to item Cite

Clinical manifestations in a large hereditary hemorrhagic telangiectasia (HHT) type 2 kindred.

Journal Article Am J Med Genet · August 14, 2000 HHT type 2 (HHT 2) is a multi-system vascular dysplasia caused by a mutation in the ALK-1 gene, but the phenotype has not been well defined. We report on 51 members of an HHT 2 kindred with an ALK-1 gene mutation shown to be associated with the disorder. T ... Full text Link to item Cite

Two common endoglin mutations in families with hereditary hemorrhagic telangiectasia in the Netherlands Antilles: evidence for a founder effect.

Journal Article Hum Genet · July 2000 Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant bleeding disorder characterized by localized angiodysplasia. Mutations in either of two genes, endoglin or ALK-1, can cause HHT. Both genes encode putative receptors for the transforming ... Full text Link to item Cite

Expression analysis of endoglin missense and truncation mutations: insights into protein structure and disease mechanisms.

Journal Article Hum Mol Genet · March 22, 2000 Hereditary hemorrhagic telangiectasia (HHT) is an inherited autosomal dominant vascular dysplasia caused by mutations in either endoglin (HHT1) or activin-like kinase receptor-1 (ALK-1) (HHT2). The majority of the mutations in endoglin cause frameshifts an ... Full text Link to item Cite

Endoglin, an ancillary TGFbeta receptor, is required for extraembryonic angiogenesis and plays a key role in heart development.

Journal Article Dev Biol · January 1, 2000 Endoglin (CD105) is expressed on the surface of endothelial and haematopoietic cells in mammals and binds TGFbeta isoforms 1 and 3 in combination with the signaling complex of TGFbeta receptors types I and II. Endoglin expression increases during angiogene ... Full text Link to item Cite

Expression analysis of four endoglin missense mutations suggests that haploinsufficiency is the predominant mechanism for hereditary hemorrhagic telangiectasia type 1.

Journal Article Hum Mol Genet · November 1999 ENDOGLIN codes for a homodimeric membrane glycoprotein that interacts with receptors for members of the TGF-beta superfamily and is the gene mutated in the autosomal dominant vascular disorder hereditary hemorrhagic telangiectasia type 1 (HHT1). We recentl ... Full text Link to item Cite

Mutations in the gene encoding KRIT1, a Krev-1/rap1a binding protein, cause cerebral cavernous malformations (CCM1).

Journal Article Hum Mol Genet · November 1999 Cerebral cavernous malformations (CCM) are congenital vascular anomalies of the brain that can cause significant neurological disabilities, including intractable seizures and hemorrhagic stroke. One locus for autosomal dominant CCM ( CCM1 ) maps to chromos ... Full text Link to item Cite

A second locus for inherited venous malformations maps to chromosome 1p.

Conference AMERICAN JOURNAL OF HUMAN GENETICS · October 1, 1999 Link to item Cite

Physical and transcript map of CCM1 candidate interval on chromosome 7q.

Conference AMERICAN JOURNAL OF HUMAN GENETICS · October 1, 1999 Link to item Cite

Allelic and locus heterogeneity in inherited venous malformations.

Journal Article Hum Mol Genet · July 1999 Venous malformations are low-flow vascular lesions consisting of disorganized thin-walled vascular channels. These can occur sporadically but also as an autosomal dominant condition termed venous malformations, cutaneous and mucosal (VMCM; OMIM 600195). In ... Full text Link to item Cite

Assignment of transforming growth factor beta1 and beta3 and a third new ligand to the type I receptor ALK-1.

Journal Article J Biol Chem · April 9, 1999 Germ line mutations in one of two distinct genes, endoglin or ALK-1, cause hereditary hemorrhagic telangiectasia (HHT), an autosomal dominant disorder of localized angiodysplasia. Both genes encode endothelial cell receptors for the transforming growth fac ... Full text Link to item Cite

Genetic mapping of a novel familial form of infantile hemangioma.

Journal Article Am J Med Genet · January 1, 1999 Infantile hemangiomas are the most common tumor of infancy, occurring with an incidence of up to 10% of all births. They are benign but highly proliferative lesions involving aberrant localized growth of capillary endothelium. Although most hemangiomas occ ... Full text Link to item Cite

Cloning of the promoter region of human endoglin, the target gene for hereditary hemorrhagic telangiectasia type 1.

Journal Article Blood · December 15, 1998 Endoglin (CD105) is a cell surface component of the transforming growth factor-beta (TGF-beta) receptor complex highly expressed by endothelial cells. Mutations in the endoglin gene are responsible for the hereditary hemorrhagic telangiectasia type 1 (HHT1 ... Link to item Cite

Genetic abnormalities in hereditary hemorrhagic telangiectasia.

Journal Article Curr Opin Hematol · September 1998 Hereditary hemorrhagic telangiectasia (HHT), or Rendu-Osler-Weber disease, is an autosomal dominant disorder of localized angiodysplasia, although it is sometimes mistakenly identified as a hemostatic disorder due to its associated characteristic bleeding. ... Full text Link to item Cite

Familial segregation of hemangiomas and vascular malformations as an autosomal dominant trait.

Journal Article Arch Dermatol · June 1998 BACKGROUND: The pathogenesis of infantile hemangiomas is not yet understood. Growth factors and hormonal and mechanical influences have been thought to affect the focal abnormal growth of endothelial cells in these lesions. However, these influences may re ... Full text Link to item Cite

Quantitative DNA pooling to increase the efficiency of linkage analysis in autosomal dominant disease.

Journal Article Hum Genet · February 1998 DNA pooling is an efficient method to rapidly perform genome-wide linkage scans in autosomal recessive diseases in inbred populations where affected individuals are likely to be homozygous for alleles near the disease gene locus. We wanted to examine wheth ... Full text Link to item Cite

A search for the ALK-1 ligand and the role of endoglin: The two HHT genes

Conference NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY · January 1, 1998 Link to item Cite

Novel missense and frameshift mutations in the activin receptor-like kinase-1 gene in hereditary hemorrhagic telangiectasia. Mutations in brief no. 164. Online.

Journal Article Hum Mutat · 1998 Hereditary hemmorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by multisystemic vascular dyplasia and recurrent hemorrhage. One of the causative genes is the activin receptor-like kinase-1 (ALK-1) gene located on chromosome 12 ... Full text Link to item Cite

Mutation and expression analysis of the endoglin gene in hereditary hemorrhagic telangiectasia reveals null alleles.

Journal Article Hum Mutat · 1998 Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant disorder characterized by multisystemic vascular dysplasia and recurrent hemorrhage from the sites of vascular lesions. Two genes have been identified for HHT. Endoglin, a TGF-beta bindin ... Full text Link to item Cite

Genetic heterogeneity in familial venous malformations syndrome (FVM)

Conference AMERICAN JOURNAL OF HUMAN GENETICS · October 1, 1997 Link to item Cite

Identification of a new member of the myotonic dystrophy protein kinase gene family.

Conference AMERICAN JOURNAL OF HUMAN GENETICS · October 1, 1997 Link to item Cite

The activin receptor-like kinase 1 gene: genomic structure and mutations in hereditary hemorrhagic telangiectasia type 2.

Journal Article Am J Hum Genet · July 1997 The activin receptor-like kinase 1 gene (ALK-1) is the second locus for the autosomal dominant vascular disease hereditary hemorrhagic telangiectasia (HHT). In this paper we present the genomic structure of the ALK-1 gene, a type I serine-threonine kinase ... Full text Link to item Cite

Endoglin gene polymorphism as a risk factor for sporadic intracerebral hemorrhage.

Journal Article Ann Neurol · May 1997 Intracerebral hemorrhage (ICH) is a common and serious type of stroke. Recent studies have shown that inherited factors that affect the development of the vessel wall can increase the risk of ICH. We studied endoglin as a candidate gene in patients with sp ... Full text Link to item Cite

Vascular dysmorphogenesis caused by an activating mutation in the receptor tyrosine kinase TIE2.

Journal Article Cell · December 27, 1996 Venous malformations (VMs), the most common errors of vascular morphogenesis in humans, are composed of dilated, serpiginous channels. The walls of the channels have a variable thickness of smooth muscle; some mural regions lack smooth muscle altogether. A ... Full text Link to item Cite

Mutations in the activin receptor-like kinase 1 gene in hereditary haemorrhagic telangiectasia type 2.

Journal Article Nat Genet · June 1996 Hereditary haemorrhagic telangiectasia, or Osler-Rendu-Weber (ORW) syndrome, is an autosomal dominant vascular dysplasia. So far, two loci have been demonstrated for ORW. Linkage studies established an ORW locus at chromosome 9q3; endoglin was subsequently ... Full text Link to item Cite

Chromosome breakpoint at 17q11.2 and insertion of DNA from three different chromosomes in a glioblastoma with exceptional glial fibrillary acidic protein expression.

Journal Article Cancer Genet Cytogenet · March 1996 A glioblastoma that retained glial fibrillary acidic protein (GFAP) in culture has a break in the long arm of chromosome 17 at band 17q11.2. DNA inserted at this breakpoint came from chromosome bands 3p21, 3q23, 16q11.2, and 22q11.2. These chromosome fragm ... Full text Link to item Cite

Clinical heterogeneity in hereditary haemorrhagic telangiectasia: are pulmonary arteriovenous malformations more common in families linked to endoglin?

Journal Article J Med Genet · March 1996 Pulmonary arteriovenous malformations (PAVMs) occur in up to 27% of patients with hereditary haemorrhagic telangiectasia (HHT) and are associated with a rate of paradoxical cerebral embolism at presentation of up to 36%. At least two different loci have be ... Full text Link to item Cite

Hereditary hemorrhagic telangiectasia - Reply

Journal Article NEW ENGLAND JOURNAL OF MEDICINE · February 1, 1996 Link to item Cite

Hereditary hemorrhagic telangiectasia.

Journal Article N Engl J Med · February 1, 1996 Link to item Cite

Identification and mapping of type 1 neurofibromatosis (NF1) homologous loci.

Journal Article Cytogenet Cell Genet · 1996 During the establishment of a YAC contig for the type 1 neurofibromatosis (NF1) region on human chromosome 17q11.2, several YAC clones were isolated which originated from a different chromosome but which retained strong homology to NF1 coding regions (Marc ... Full text Link to item Cite

Somatic mutations in the neurofibromatosis 1 gene in gliomas and primitive neuroectodermal tumours

Journal Article Anticancer Research · December 1, 1995 The increased frequency of glioma among neurofibromatosis 1 (NF1) patients suggests a general involvement of the NF1 gene in glioma tumourigenesis. Using the methodology of conventional Southern blotting with a complete panel of overlapping partial cDNAs c ... Cite

Refined localization of the cerebral cavernous malformation gene (CCM1) to a 4-cM interval of chromosome 7q contained in a well-defined YAC contig.

Journal Article Genome Res · November 1995 Cerebral cavernous malformations (CCM) are vascular lesions present in some 20 million people worldwide that are responsible for seizures, migraine, hemorrhage, and other neurologic problems. Familial cases ofCCM can be inherited as an autosomal dominant d ... Full text Link to item Cite

Hereditary hemorrhagic telangiectasia.

Journal Article N Engl J Med · October 5, 1995 Full text Link to item Cite

A 2ND LOCUS FOR HEREDITARY HEMORRHAGIC TELANGIECTASIA MAPS TO CHROMOSOME-12

Conference AMERICAN JOURNAL OF HUMAN GENETICS · October 1, 1995 Link to item Cite

Report and abstracts of the 4th International Workshop on Chromosome 9. Williamsburg, Virginia, USA, April 23-25, 1995.

Journal Article Ann Hum Genet · October 1995 The Fourth International Workshop on Chromosome 9 was a highly successful endeavor in terms of the growth of the map, both genetic and physical, the amount of data entered into GDB, and the continued comradeship in the sharing of data and resources that wa ... Link to item Cite

A second locus for hereditary hemorrhagic telangiectasia maps to chromosome 12.

Journal Article Genome Res · August 1995 Hereditary hemorrhagic telangiectasia (HHT) or Osler-Rendu-Weber (ORW) disease is an autosomal dominant vascular dysplasia. Initial linkage studies identified an ORW gene localized to 9q33-q34 but with some families clearly excluding this region. A probabl ... Full text Link to item Cite

A locus for cerebral cavernous malformations maps to chromosome 7q in two families.

Journal Article Genomics · July 20, 1995 Cavernous malformations (angiomas) affecting the central nervous system and retina can be inherited in autosomal dominant pattern (OMIM 116860). These vascular lesions may remain clinically silent or lead to a number of neurological symptoms including seiz ... Full text Link to item Cite

A gene for familial venous malformations maps to chromosome 9p in a second large kindred.

Journal Article J Med Genet · March 1995 Venous malformations are a common form of vascular anomaly that cause pain and disfigurement and can be life threatening if they involve critical organs. They occur sporadically or in a familial form, where multiple lesions are usually present. We have ide ... Full text Link to item Cite

COL5A1: fine genetic mapping and exclusion as candidate gene in families with nail-patella syndrome, tuberous sclerosis 1, hereditary hemorrhagic telangiectasia, and Ehlers-Danlos Syndrome type II.

Journal Article Genomics · February 10, 1995 COL5A1, the gene for the alpha 1 chain of type V collagen, has been considered a candidate gene for certain diseases based on chromosomal location and/or disease phenotype. We have employed 3'-untranslated region RFLPs to exclude COL5A1 as a candidate gene ... Full text Link to item Cite

Somatic mutations in the neurofibromatosis 1 gene in gliomas and primitive neuroectodermal tumours.

Journal Article Anticancer Res · 1995 The increased frequency of glioma among neurofibromatosis 1 (NF1) patients suggests a general involvement of the NF1 gene in glioma tumourigenesis. Using the methodology of conventional Southern blotting with a complete panel of overlapping partial cDNAs c ... Link to item Cite

Genetic heterogeneity in hereditary haemorrhagic telangiectasia: possible correlation with clinical phenotype.

Journal Article J Med Genet · December 1994 Hereditary haemorrhagic telangiectasia (HHT) or Osler-Weber-Rendu syndrome is an autosomal dominant vascular dysplasia characterised by recurrent haemorrhage. Our initial linkage studies found an HHT gene to be localised to 9q3 in two large kindreds. In th ... Full text Link to item Cite

Endoglin, a TGF-beta binding protein of endothelial cells, is the gene for hereditary haemorrhagic telangiectasia type 1.

Journal Article Nat Genet · December 1994 Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by multisystemic vascular dysplasia and recurrent haemorrhage. Linkage for some families has been established to chromosome 9q33-q34. In the present study, endogli ... Full text Link to item Cite

Genetic heterogeneity in hereditary haemorrhagic telangiectasia.

Journal Article J Med Genet · December 1994 A locus causing hereditary haemorrhagic telangiectasia (HHT) has recently been mapped to 9q34 in four families and designated HHT1. In this paper, the results of a linkage study showing genetic heterogeneity in four families in whom HHT is segregating are ... Full text Link to item Cite

A disease locus for hereditary haemorrhagic telangiectasia maps to chromosome 9q33-34.

Journal Article Nat Genet · February 1994 Hereditary haemorrhagic telangiectasia (HHT), or Osler-Weber-Rendu disease, is an autosomal dominant vascular dysplasia of unknown pathogenesis leading to 'widespread' dermal, mucosal and visceral telangiectases and recurrent haemorrhage. We have mapped th ... Full text Link to item Cite

An EcoRI RFLP in the 5' region of the human NF1 gene.

Journal Article Hum Genet · December 1993 Von Recklinghausen neurofibromatosis or type 1 neurofibromatosis (NF1), is one of the most common autosomal dominant disorders. NF1 is characterized by neurofibromas, cafĂ©-au-lait spots and Lisch nodules of the iris. The NF1 gene is located in 17q11.2. The ... Full text Link to item Cite

Analysis of the neurofibromatosis type 1 (NF1) GAP-related domain by site-directed mutagenesis.

Journal Article Oncogene · March 1993 The gene for von Recklinghausen neurofibromatosis type 1 (NF1) was recently identified by positional cloning and found to encode a protein with sequence similarity to a family of eucaryotic GTPase-activating proteins (GAPs). Expression of the NF1-GAP-relat ... Link to item Cite

Somatic deletion of the neurofibromatosis type 1 gene in a neurofibrosarcoma supports a tumour suppressor gene hypothesis.

Journal Article Nat Genet · February 1993 Individuals with neurofibromatosis type 1 (NF1) have an increased risk of developing benign and malignant tumours. The NF1 gene is thought to be a tumour suppressor gene, yet no direct proof at the molecular level exists to support this hypothesis. Here we ... Full text Link to item Cite

A conserved alternative splice in the von Recklinghausen neurofibromatosis (NF1) gene produces two neurofibromin isoforms, both of which have GTPase-activating protein activity.

Journal Article Mol Cell Biol · January 1993 Sequence analysis has shown significant homology between the catalytic regions of the mammalian ras GTPase-activating protein (GAP), yeast Ira1p and Ira2p (inhibitory regulators of the RAS-cyclic AMP pathway), and neurofibromin, the protein encoded by the ... Full text Link to item Cite

The gene for a novel epidermal antigen maps near the neurofibromatosis 1 gene.

Journal Article Genomics · October 1992 Recently the M17S1 gene, encoding an epidermal antigen thought to play a role in cell adhesion, was mapped to chromosome bands 17q11-q12, placing it in the vicinity of the gene for the genetic disorder neurofibromatosis 1 (NF1). The pleomorphic cutaneous l ... Full text Link to item Cite

NF1-related locus on chromosome 15.

Journal Article Genomics · August 1992 A neurofibromatosis type I (NF1)-related locus has been identified on chromosome 15. It contains a partial copy of the NF1 GAP-related domain, which is known to interact with the ras protooncogenes. However, the chromosome 15 sequence contains multiple del ... Full text Link to item Cite

A yeast artificial chromosome contig encompassing the type 1 neurofibromatosis gene.

Journal Article Genomics · July 1992 The yeast artificial chromosome (YAC) system (Burke et al., 1987, Science 236: 806-812) allows the direct cloning of large regions of the genome. A YAC contig map of approximately 700 kb encompassing the region surrounding the type 1 neurofibromatosis (NF1 ... Full text Link to item Cite

Sequencing and analysis of genomic fragments from the NF1 locus.

Journal Article DNA Seq · 1992 The sequence of five non-contiguous genomic fragments encompassing 14.4 kilobases from the NF1 locus have been determined by fluorescence-based automated DNA sequence analysis. These fragments included one kilobase of the NF1 coding region, which resulted ... Full text Link to item Cite

cDNA cloning of the type 1 neurofibromatosis gene: complete sequence of the NF1 gene product.

Journal Article Genomics · December 1991 Von Recklinghausen neurofibromatosis, or type 1 neurofibromatosis (NF1), is a common autosomal dominant disorder characterized by abnormalities in multiple tissues derived from the embryonic neural crest. Portions of the gene have been recently identified ... Full text Link to item Cite

A highly polymorphic cDNA probe in the NF1 gene.

Journal Article Nucleic Acids Res · July 11, 1991 Full text Link to item Cite

cDNA sequence and genomic structure of EV12B, a gene lying within an intron of the neurofibromatosis type 1 gene.

Journal Article Genomics · March 1991 The gene responsible for neurofibromatosis type 1 (NF1), one of the more common inherited human disorders, was identified recently, and segments of it were cloned. Two translocation breakpoints that interrupt the NF1 gene in NF1 patients flank a 60-kb segm ... Full text Link to item Cite

Type 1 neurofibromatosis gene: correction.

Journal Article Science · December 21, 1990 Link to item Cite

A 90 kb DNA deletion associated with neurofibromatosis type 1.

Journal Article J Med Genet · December 1990 A deletion of 90 kb of DNA has been identified in a patient with neurofibromatosis type 1, using pulsed field gel electrophoresis. The deletion lies between probes 17L1A and AC5 in the critical region of chromosome 17 and represents the only molecular alte ... Full text Link to item Cite

The NF1 locus encodes a protein functionally related to mammalian GAP and yeast IRA proteins.

Journal Article Cell · November 16, 1990 The von Recklinghausen neurofibromatosis locus, NF1, encodes a protein with homology restricted to the catalytic region of the RAS GTPase-activating protein, GAP, and with extensive homology to the IRA1 and IRA2 gene products of the yeast S. cerevisiae. A ... Full text Link to item Cite

A chromosome jump crosses a translocation breakpoint in the von Recklinghausen neurofibromatosis region.

Journal Article Genes Chromosomes Cancer · November 1990 The von Recklinghausen neurofibromatosis (NFI) gene has been previously localized to the region 17q11.2 by genetic analysis. Consistent with this, two NFI patients have been described with autosomal translocations with breakpoints in 17q11.2, and these rep ... Full text Link to item Cite

Type 1 neurofibromatosis gene: identification of a large transcript disrupted in three NF1 patients.

Journal Article Science · July 13, 1990 Von Recklinghausen neurofibromatosis (NF1) is a common autosomal dominant disorder characterized by abnormalities in multiple tissues derived from the neural crest. No reliable cellular phenotypic marker has been identified, which has hampered direct effor ... Full text Link to item Cite

Three tightly linked genes encoding human type I keratins: conservation of sequence in the 5'-untranslated leader and 5'-upstream regions of coexpressed keratin genes.

Journal Article Mol Cell Biol · February 1986 We have isolated and subcloned three separate segments of human DNA which share strong sequence homology with a previously sequenced gene encoding a type I keratin, K14 (50 kilodaltons). Restriction endonuclease mapping has demonstrated that these three ge ... Full text Link to item Cite

Complete sequence of a gene encoding a human type I keratin: sequences homologous to enhancer elements in the regulatory region of the gene.

Journal Article Proc Natl Acad Sci U S A · March 1985 We report here the complete nucleotide sequence of a gene encoding the 50-kDa keratin expressed in abundance in human epidermal cells. According to its sequence, this gene has a single transcriptional initiation site and a single polyadenylylation signal. ... Full text Link to item Cite

Remarkable conservation of structure among intermediate filament genes.

Journal Article Cell · December 1984 Using a cloned cDNA complementary to a portion of the mRNA for the 50 kd human epidermal keratin, we have screened a human genomic library and have isolated and sequenced the gene encoding this keratin. A comparison of the keratin gene with the very distan ... Full text Link to item Cite

Expression of unusually large keratins during terminal differentiation: balance of type I and type II keratins is not disrupted.

Journal Article J Cell Biol · November 1984 When a basal epidermal cell undergoes a commitment to terminally differentiate, it ceases to divide and begins to migrate outward towards the surface of the skin. Dramatic changes in its cytoskeletal architecture take place, accompanied by numerous changes ... Full text Link to item Cite

Type I and type II keratins have evolved from lower eukaryotes to form the epidermal intermediate filaments in mammalian skin.

Journal Article Proc Natl Acad Sci U S A · October 1983 We have traced the evolutionary origins of keratin-like sequences to the genomes of lower eukaryotes. The proteins encoded by these genes have evolved to form the intermediate filaments that comprise the backbone of vertebrate skin cells. Two related but d ... Full text Link to item Cite