Marie Theresa McDonald

Journal Article Eur J Hum Genet · April 27, 2024 Bryant-Li-Bhoj syndrome (BLBS), which became OMIM-classified in 2022 (OMIM: 619720, 619721), is caused by germline variants in the two genes that encode histone H3.3 (H3-3A/H3F3A and H3-3B/H3F3B) [1-4]. This syndrome is characterized by developmental delay ... Full text Link to item Cite

The severity of MUSK pathogenic variants is predicted by the protein domain they disrupt.

Journal Article HGG Adv · April 1, 2024 Biallelic loss-of-function variants in the MUSK gene result in two allelic disorders: (1) congenital myasthenic syndrome (CMS; OMIM: 616325), a neuromuscular disorder that has a range of severity from severe neonatal-onset weakness to mild adult-onset weak ... Full text Link to item Cite

Genomic analyses in Cornelia de Lange Syndrome and related diagnoses: Novel candidate genes, genotype-phenotype correlations and common mechanisms.

Journal Article Am J Med Genet A · August 2023 Cornelia de Lange Syndrome (CdLS) is a rare, dominantly inherited multisystem developmental disorder characterized by highly variable manifestations of growth and developmental delays, upper limb involvement, hypertrichosis, cardiac, gastrointestinal, cran ... Full text Link to item Cite

The SHDRA syndrome-associated gene TMEM260 encodes a protein-specific O-mannosyltransferase.

Journal Article Proc Natl Acad Sci U S A · May 23, 2023 Mutations in the TMEM260 gene cause structural heart defects and renal anomalies syndrome, but the function of the encoded protein remains unknown. We previously reported wide occurrence of O-mannose glycans on extracellular immunoglobulin, plexin, transcr ... Full text Link to item Cite

Single substitution in H3.3G34 alters DNMT3A recruitment to cause progressive neurodegeneration.

Journal Article Cell · March 16, 2023 Germline histone H3.3 amino acid substitutions, including H3.3G34R/V, cause severe neurodevelopmental syndromes. To understand how these mutations impact brain development, we generated H3.3G34R/V/W knock-in mice and identified strikingly distinct developm ... Full text Link to item Cite

Neurodevelopmental and Epilepsy Phenotypes in Individuals With Missense Variants in the Voltage-Sensing and Pore Domains of KCNH5.

Journal Article Neurology · February 7, 2023 BACKGROUND AND OBJECTIVES: KCNH5 encodes the voltage-gated potassium channel EAG2/Kv10.2. We aimed to delineate the neurodevelopmental and epilepsy phenotypic spectrum associated with de novo KCNH5 variants. METHODS: We screened 893 individuals with develo ... Full text Link to item Cite

A recurrent, de novo pathogenic variant in ARPC4 disrupts actin filament formation and causes microcephaly and speech delay

Journal Article Human Genetics and Genomics Advances · January 13, 2022 We report seven affected individuals from six families with a recurrent, de novo variant in the ARPC4 gene (c.472C>T [p.Arg158Cys (GenBank: NM_005718.4)]). Core features in affected individuals include microcephaly, mild motor delays, and significant speec ... Full text Cite

Novel pathogenic variants and quantitative phenotypic analyses of Robinow syndrome: WNT signaling perturbation and phenotypic variability.

Journal Article HGG Adv · January 13, 2022 Robinow syndrome (RS) is a genetically heterogeneous disorder with six genes that converge on the WNT/planar cell polarity (PCP) signaling pathway implicated (DVL1, DVL3, FZD2, NXN, ROR2, and WNT5A). RS is characterized by skeletal dysplasia and distinctiv ... Full text Link to item Cite

Interference of nuclear mitochondrial DNA segments in mitochondrial DNA testing resembles biparental transmission of mitochondrial DNA in humans.

Journal Article Genet Med · August 2021 PURPOSE: Reports have questioned the dogma of exclusive maternal transmission of human mitochondrial DNA (mtDNA), including the recent report of an admixture of two mtDNA haplogroups in individuals from three multigeneration families. This was interpreted ... Full text Link to item Cite

Haploinsufficiency of PRR12 causes a spectrum of neurodevelopmental, eye, and multisystem abnormalities.

Journal Article Genet Med · July 2021 PURPOSE: Proline Rich 12 (PRR12) is a gene of unknown function with suspected DNA-binding activity, expressed in developing mice and human brains. Predicted loss-of-function variants in this gene are extremely rare, indicating high intolerance of haploinsu ... Full text Link to item Cite

Pathogenic SPTBN1 variants cause an autosomal dominant neurodevelopmental syndrome.

Journal Article Nat Genet · July 2021 SPTBN1 encodes βII-spectrin, the ubiquitously expressed β-spectrin that forms micrometer-scale networks associated with plasma membranes. Mice deficient in neuronal βII-spectrin have defects in cortical organization, developmental delay and behavioral defi ... Full text Link to item Cite

Severe multisystem pathology, metabolic acidosis, mitochondrial dysfunction, and early death associated with an X-linked AIFM1 variant.

Journal Article Cold Spring Harb Mol Case Stud · June 2021 Variants in the X-linked gene AIFM1 (apoptosis-inducing factor mitochondria-associated 1) are associated with a highly variable clinical presentation that encompasses motor neuropathy, ataxia, encephalopathies, deafness, and cognitive impairment. AIFM1 enc ... Full text Link to item Cite

De novo variants in SNAP25 cause an early-onset developmental and epileptic encephalopathy.

Conference Genet Med · April 2021 PURPOSE: This study aims to provide a comprehensive description of the phenotypic and genotypic spectrum of SNAP25 developmental and epileptic encephalopathy (SNAP25-DEE) by reviewing newly identified and previously reported individuals. METHODS: Individua ... Full text Link to item Cite

Correction to: De novo variants in SNAP25 cause an early-onset developmental and epileptic encephalopathy.

Journal Article Genet Med · April 2021 Full text Link to item Cite

An Unusual Association: Total Anomalous Pulmonary Venous Return and Aortic Arch Obstruction in Patients with Cat Eye Syndrome.

Journal Article J Pediatr Genet · March 2021 Cat eye syndrome (CES) is a rare genetic defect, characterized by iris colobomas, preauricular skin tags, and anal malformations. Affecting 1 in 150,000 people, this defect is caused by duplication or triplication of the proximal long (q) arm of chromosome ... Full text Link to item Cite

Early onset severe ATP1A2 epileptic encephalopathy: Clinical characteristics and underlying mutations.

Journal Article Epilepsy Behav · March 2021 BACKGROUND: ATP1A2 mutations cause hemiplegic migraine with or without epilepsy or acute reversible encephalopathy. Typical onset is in adulthood or older childhood without subsequent severe long-term developmental impairments. AIM: We aimed to describe th ... Full text Open Access Link to item Cite

A relatively common homozygous TRAPPC4 splicing variant is associated with an early-infantile neurodegenerative syndrome.

Journal Article Eur J Hum Genet · February 2021 Trafficking protein particle (TRAPP) complexes, which include the TRAPPC4 protein, regulate membrane trafficking between lipid organelles in a process termed vesicular tethering. TRAPPC4 was recently implicated in a recessive neurodevelopmental condition i ... Full text Link to item Cite

Phenotypic target organ and biomarker variation within a family with late onset Fabry disease

Conference Molecular Genetics and Metabolism · February 2021 Full text Cite

Germline AGO2 mutations impair RNA interference and human neurological development.

Journal Article Nat Commun · November 16, 2020 ARGONAUTE-2 and associated miRNAs form the RNA-induced silencing complex (RISC), which targets mRNAs for translational silencing and degradation as part of the RNA interference pathway. Despite the essential nature of this process for cellular function, th ... Full text Link to item Cite

NCKAP1 Disruptive Variants Lead to a Neurodevelopmental Disorder with Core Features of Autism.

Journal Article Am J Hum Genet · November 5, 2020 NCKAP1/NAP1 regulates neuronal cytoskeletal dynamics and is essential for neuronal differentiation in the developing brain. Deleterious variants in NCKAP1 have been identified in individuals with autism spectrum disorder (ASD) and intellectual disability; ... Full text Link to item Cite

Expanded phenotypic spectrum of neurodevelopmental and neurodegenerative disorder Bryant-Li-Bhoj syndrome with 38 additional individuals.

The severity of MUSK pathogenic variants is predicted by the protein domain they disrupt.

Genomic analyses in Cornelia de Lange Syndrome and related diagnoses: Novel candidate genes, genotype-phenotype correlations and common mechanisms.

The SHDRA syndrome-associated gene TMEM260 encodes a protein-specific O-mannosyltransferase.

Single substitution in H3.3G34 alters DNMT3A recruitment to cause progressive neurodegeneration.

Neurodevelopmental and Epilepsy Phenotypes in Individuals With Missense Variants in the Voltage-Sensing and Pore Domains of KCNH5.

A recurrent, de novo pathogenic variant in ARPC4 disrupts actin filament formation and causes microcephaly and speech delay

Novel pathogenic variants and quantitative phenotypic analyses of Robinow syndrome: WNT signaling perturbation and phenotypic variability.

Interference of nuclear mitochondrial DNA segments in mitochondrial DNA testing resembles biparental transmission of mitochondrial DNA in humans.

Haploinsufficiency of PRR12 causes a spectrum of neurodevelopmental, eye, and multisystem abnormalities.

Pathogenic SPTBN1 variants cause an autosomal dominant neurodevelopmental syndrome.

Severe multisystem pathology, metabolic acidosis, mitochondrial dysfunction, and early death associated with an X-linked AIFM1 variant.

De novo variants in SNAP25 cause an early-onset developmental and epileptic encephalopathy.

Correction to: De novo variants in SNAP25 cause an early-onset developmental and epileptic encephalopathy.

Journal Article Genet Med · April 2021 Full text Link to item Cite

An Unusual Association: Total Anomalous Pulmonary Venous Return and Aortic Arch Obstruction in Patients with Cat Eye Syndrome.

Early onset severe ATP1A2 epileptic encephalopathy: Clinical characteristics and underlying mutations.

A relatively common homozygous TRAPPC4 splicing variant is associated with an early-infantile neurodegenerative syndrome.

Phenotypic target organ and biomarker variation within a family with late onset Fabry disease

Conference Molecular Genetics and Metabolism · February 2021 Full text Cite

Germline AGO2 mutations impair RNA interference and human neurological development.

NCKAP1 Disruptive Variants Lead to a Neurodevelopmental Disorder with Core Features of Autism.

A Gain-of-Function Mutation in KCNMA1 Causes Dystonia Spells Controlled With Stimulant Therapy.

Journal Article Mov Disord · October 2020 BACKGROUND: The mutations of KCNMA1 BK-type K+ channel have been identified in patients with various movement disorders. The underlying pathophysiology and corresponding therapeutics are lacking. OBJECTIVES: To report our clinical and biophysical character ... Full text Link to item Cite

Biallelic variants in PPP1R13L cause paediatric dilated cardiomyopathy.

Journal Article Clin Genet · October 2020 Childhood dilated cardiomyopathy (DCM) is a leading cause of heart failure requiring cardiac transplantation and approximately 5% of cases result in sudden death. Knowledge of the underlying genetic cause can aid prognostication and clinical management and ... Full text Link to item Cite

A pathogenic variant in the SETBP1 hotspot results in a forme-fruste Schinzel-Giedion syndrome.

Journal Article Am J Med Genet A · August 2020 Schinzel-Giedion syndrome (SGS; OMIM 269150) is an ultra-rare genetic disorder associated with a distinctive facial gestalt, congenital malformations, severe intellectual disability, and a progressive neurological course. The prognosis for SGS is poor, wit ... Full text Link to item Cite

Alternative transcripts in variant interpretation: the potential for missed diagnoses and misdiagnoses.

Journal Article Genet Med · July 2020 PURPOSE: Guidelines by professional organizations for assessing variant pathogenicity include the recommendation to utilize biologically relevant transcripts; however, there is variability in transcript selection by laboratories. METHODS: We describe three ... Full text Link to item Cite

Phenotypic spectrum and transcriptomic profile associated with germline variants in TRAF7.

Journal Article Genet Med · July 2020 PURPOSE: Somatic variants in tumor necrosis factor receptor-associated factor 7 (TRAF7) cause meningioma, while germline variants have recently been identified in seven patients with developmental delay and cardiac, facial, and digital anomalies. We aimed ... Full text Link to item Cite

A comprehensive testing algorithm for the diagnosis of Fabry disease in males and females.

Journal Article Mol Genet Metab · July 2020 PURPOSE: Successful diagnosis of Fabry disease is often delayed or missed in patients, especially females, due to clinical heterogeneity and a lack of disease awareness. We present our experience testing for Fabry disease in high risk populations and discu ... Full text Link to item Cite

De Novo SOX6 Variants Cause a Neurodevelopmental Syndrome Associated with ADHD, Craniosynostosis, and Osteochondromas.

Journal Article Am J Hum Genet · June 4, 2020 SOX6 belongs to a family of 20 SRY-related HMG-box-containing (SOX) genes that encode transcription factors controlling cell fate and differentiation in many developmental and adult processes. For SOX6, these processes include, but are not limited to, neur ... Full text Link to item Cite

CSGALNACT1-congenital disorder of glycosylation: A mild skeletal dysplasia with advanced bone age.

Journal Article Hum Mutat · March 2020 Congenital disorders of glycosylation (CDGs) comprise a large number of inherited metabolic defects that affect the biosynthesis and attachment of glycans. CDGs manifest as a broad spectrum of disease, most often including neurodevelopmental and skeletal a ... Full text Link to item Cite

Epileptic encephalopathy with features of rapid-onset dystonia Parkinsonism and alternating hemiplegia of childhood: a novel combination phenotype associated with ATP1A3 mutation.

Journal Article Epileptic Disord · February 1, 2020 Mutations in ATP1A3 have been found to cause rapid-onset dystonia Parkinsonism, alternating hemiplegia of childhood, epileptic encephalopathy and other syndromes. We report a four-year, nine-month-old boy with episodes of frequent and recurrent status epil ... Full text Link to item Cite

A Genocentric Approach to Discovery of Mendelian Disorders.

Journal Article Am J Hum Genet · November 7, 2019 The advent of inexpensive, clinical exome sequencing (ES) has led to the accumulation of genetic data from thousands of samples from individuals affected with a wide range of diseases, but for whom the underlying genetic and molecular etiology of their cli ... Full text Open Access Link to item Cite

HIST1H1E heterozygous protein-truncating variants cause a recognizable syndrome with intellectual disability and distinctive facial gestalt: A study to clarify the HIST1H1E syndrome phenotype in 30 individuals.

Journal Article Am J Med Genet A · October 2019 Histone Gene Cluster 1 Member E, HIST1H1E, encodes Histone H1.4, is one of a family of epigenetic regulator genes, acts as a linker histone protein, and is responsible for higher order chromatin structure. HIST1H1E syndrome (also known as Rahman syndrome, ... Full text Link to item Cite

Haploinsufficiency of the Notch Ligand DLL1 Causes Variable Neurodevelopmental Disorders.

Journal Article Am J Hum Genet · September 5, 2019 Notch signaling is an established developmental pathway for brain morphogenesis. Given that Delta-like 1 (DLL1) is a ligand for the Notch receptor and that a few individuals with developmental delay, intellectual disability, and brain malformations have mi ... Full text Link to item Cite

A case report of mevalonate kinase deficiency in a 14-month-old female with fevers and lower extremity weakness.

Journal Article BMC Pediatr · July 20, 2019 BACKGROUND: This case follows a 14-month-old female, who despite multiple presentations to several physicians, continued to have recurrent febrile episodes with gross motor delay. Her case revealed an often missed diagnosis of Mevalonate Kinase Deficiency, ... Full text Open Access Link to item Cite

Corrigendum to "Does age affect response to quinidine in patients with KCNT1 mutations? Report of three new cases and review of the literature" [Seizure 55 (February) (2018) 1-3].

Journal Article Seizure · July 2019 Full text Link to item Cite

Expanding the clinical phenotype of individuals with a 3-bp in-frame deletion of the NF1 gene (c.2970_2972del): an update of genotype-phenotype correlation.

Journal Article Genet Med · April 2019 PURPOSE: Neurofibromatosis type 1 (NF1) is characterized by a highly variable clinical presentation, but almost all NF1-affected adults present with cutaneous and/or subcutaneous neurofibromas. Exceptions are individuals heterozygous for the NF1 in-frame d ... Full text Link to item Cite

De Novo Pathogenic Variants in CACNA1E Cause Developmental and Epileptic Encephalopathy with Contractures, Macrocephaly, and Dyskinesias.

Journal Article Am J Hum Genet · March 7, 2019 Full text Open Access Link to item Cite

Correction: Expanding the clinical phenotype of individuals with a 3-bp in-frame deletion of the NF1 gene (c.2970_2972del): an update of genotype-phenotype correlation.

Journal Article Genet Med · March 2019 A correction has been published to this Article. The PDF and HTML have been updated accordingly. ... Full text Link to item Cite

Recessive Rare Variants in Deoxyhypusine Synthase, an Enzyme Involved in the Synthesis of Hypusine, Are Associated with a Neurodevelopmental Disorder.

Journal Article Am J Hum Genet · February 7, 2019 Hypusine is formed post-translationally from lysine and is found in a single cellular protein, eukaryotic translation initiation factor-5A (eIF5A), and its homolog eIF5A2. Biosynthesis of hypusine is a two-step reaction involving the enzymes deoxyhypusine ... Full text Link to item Cite

Cornelia de Lange syndrome in diverse populations.

Journal Article Am J Med Genet A · February 2019 Cornelia de Lange syndrome (CdLS) is a dominant multisystemic malformation syndrome due to mutations in five genes-NIPBL, SMC1A, HDAC8, SMC3, and RAD21. The characteristic facial dysmorphisms include microcephaly, arched eyebrows, synophrys, short nose wit ... Full text Link to item Cite

Mutations in NCAPG2 Cause a Severe Neurodevelopmental Syndrome that Expands the Phenotypic Spectrum of Condensinopathies.

Journal Article Am J Hum Genet · January 3, 2019 The use of whole-exome and whole-genome sequencing has been a catalyst for a genotype-first approach to diagnostics. Under this paradigm, we have implemented systematic sequencing of neonates and young children with a suspected genetic disorder. Here, we r ... Full text Open Access Link to item Cite

Biallelic mutations in FDXR cause neurodegeneration associated with inflammation.

Journal Article J Hum Genet · December 2018 Mitochondrial dysfunction lies behind many neurodegenerative disorders, owing largely to the intense energy requirements of most neurons. Such mitochondrial dysfunction may work through a variety of mechanisms, from direct disruption of the electron transp ... Full text Link to item Cite

Further evidence for the involvement of EFL1 in a Shwachman-Diamond-like syndrome and expansion of the phenotypic features.

Journal Article Cold Spring Harb Mol Case Stud · October 2018 Recent evidence has implicated EFL1 in a phenotype overlapping Shwachman-Diamond syndrome (SDS), with the functional interplay between EFL1 and the previously known causative gene SBDS accounting for the similarity in clinical features. Relatively little i ... Full text Link to item Cite

Functional variants in TBX2 are associated with a syndromic cardiovascular and skeletal developmental disorder.

Journal Article Hum Mol Genet · July 15, 2018 The 17 genes of the T-box family are transcriptional regulators that are involved in all stages of embryonic development, including craniofacial, brain, heart, skeleton and immune system. Malformation syndromes have been linked to many of the T-box genes. ... Full text Link to item Cite

Dual Molecular Effects of Dominant RORA Mutations Cause Two Variants of Syndromic Intellectual Disability with Either Autism or Cerebellar Ataxia.

Journal Article Am J Hum Genet · May 3, 2018 RORα, the RAR-related orphan nuclear receptor alpha, is essential for cerebellar development. The spontaneous mutant mouse staggerer, with an ataxic gait caused by neurodegeneration of cerebellar Purkinje cells, was discovered two decades ago to result fro ... Full text Link to item Cite

Does age affect response to quinidine in patients with KCNT1 mutations? Report of three new cases and review of the literature.

Journal Article Seizure · February 2018 PURPOSE: Gain-of-function mutations in the KCNT1 gene have been reported in a number of drug resistant epilepsy syndromes including Epilepsy of Infancy with Migrating Focal Seizures. Quinidine, a potassium channel blocker, has been proposed as a potential ... Full text Link to item Cite

Hemimegalencephaly with Bannayan-Riley-Ruvalcaba syndrome.

Journal Article Epileptic Disord · February 1, 2018 Hemimegalencephaly is known to occur in Proteus syndrome, but has not been reported, to our knowledge, in the other PTEN mutation-related syndrome of Bannayan-Riley-Ruvalcaba. Here, we report a patient with Bannayan-Riley-Ruvalcaba syndrome who also had he ... Full text Link to item Cite

Early Diagnosed and Treated Glutaric Acidemia Type 1 Female Presenting with Subependymal Nodules in Adulthood.

Chapter · 2018 Glutaric acidemia type 1 (GA-1, OMIM no. 231670) is an autosomal recessive disorder caused by the deficiency of glutaryl-CoA dehydrogenase (GCDH). The subsequent accumulation of the amino acids lysine, hydroxylysine, and tryptophan and their breakdown inte ... Full text Link to item Cite

Mutations in Fibronectin Cause a Subtype of Spondylometaphyseal Dysplasia with "Corner Fractures".

Journal Article Am J Hum Genet · November 2, 2017 Fibronectin is a master organizer of extracellular matrices (ECMs) and promotes the assembly of collagens, fibrillin-1, and other proteins. It is also known to play roles in skeletal tissues through its secretion by osteoblasts, chondrocytes, and mesenchym ... Full text Link to item Cite

Neuro-oculo-cutaneous cavernous hemangiomas: a CCM1 mutation-associated phakomatosis.

Journal Article J AAPOS · October 2017 Evaluation for intracranial lesions in a patient with retinal cavernous hemangiomas is vital for early recognition of this heritable and potentially life-threatening disease. We report a case of a highly penetrant but variably expressed form of cerebral ca ... Full text Link to item Cite

Association of the missense variant p.Arg203Trp in PACS1 as a cause of intellectual disability and seizures.

Journal Article Clin Genet · August 2017 Graphical abstract key: ADHD, attention deficit hyperactivity disorder; ASD, atrial septal defect; DD, developmental delay; EEG, electroencephalogram; Ht, height; ID, intellectual disability; OCD, obsessive-compulsive disorder; OFC, open fontanelle; PDA, p ... Full text Link to item Cite

Identification of EPCAM mutation: clinical use of microarray.

Journal Article Clin Case Rep · June 2017 We report a case of an infant with congenital tufting enteropathy (CTE) who presented with severe failure to thrive despite multiple interventions. This study illustrates that CTE may be missed by endoscopy, and the use of chromosomal microarray and immuno ... Full text Link to item Cite

Novel pathogenic variants in FOXP3 in fetuses with echogenic bowel and skin desquamation identified by ultrasound.

Journal Article Am J Med Genet A · May 2017 Immunodysregulation, Polyendocrinopathy, Enteropathy, X-linked (IPEX) syndrome is a rare, X-linked recessive disease that affects regulatory T cells (Tregs) resulting in diarrhea, enteropathy, eczema, and insulin-dependent diabetes mellitus. IPEX syndrome ... Full text Link to item Cite

A Recurrent De Novo Variant in NACC1 Causes a Syndrome Characterized by Infantile Epilepsy, Cataracts, and Profound Developmental Delay.

Journal Article Am J Hum Genet · February 2, 2017 Whole-exome sequencing (WES) has increasingly enabled new pathogenic gene variant identification for undiagnosed neurodevelopmental disorders and provided insights into both gene function and disease biology. Here, we describe seven children with a neurode ... Full text Link to item Cite

Practical considerations in the clinical application of whole-exome sequencing.

Journal Article Clin Genet · February 2016 Despite the exciting advent of whole-exome sequencing (WES) in medical genetics practices, the optimal interpretation of results requires further actions such as reconsidering clinical information and obtaining further laboratory testing. There are no publ ... Full text Link to item Cite

An open-label clinical trial of agalsidase alfa enzyme replacement therapy in children with Fabry disease who are naïve to enzyme replacement therapy.

Journal Article Drug Des Devel Ther · 2016 BACKGROUND: Following a drug manufacturing process change, safety/efficacy of agalsidase alfa were evaluated in enzyme replacement therapy (ERT)-naïve children with Fabry disease. METHODS: In an open-label, multicenter, Phase II study (HGT-REP-084; Shire), ... Full text Link to item Cite

High Incidence of Noonan Syndrome Features Including Short Stature and Pulmonic Stenosis in Patients carrying NF1 Missense Mutations Affecting p.Arg1809: Genotype-Phenotype Correlation.

Journal Article Hum Mutat · November 2015 Neurofibromatosis type 1 (NF1) is one of the most frequent genetic disorders, affecting 1:3,000 worldwide. Identification of genotype-phenotype correlations is challenging because of the wide range clinical variability, the progressive nature of the disord ... Full text Link to item Cite

De novo mutations in KIF1A cause progressive encephalopathy and brain atrophy.

Journal Article Ann Clin Transl Neurol · June 2015 OBJECTIVE: To determine the cause and course of a novel syndrome with progressive encephalopathy and brain atrophy in children. METHODS: Clinical whole-exome sequencing was performed for global developmental delay and intellectual disability; some patients ... Full text Link to item Cite

Adult surgical experience with Loeys-Dietz syndrome.

Journal Article Ann Thorac Surg · April 2015 BACKGROUND: Loeys-Dietz syndrome (LDS) results from mutations in receptors for the cytokine transforming growth factor-β leading to aggressive aortic pathology sometimes accompanied by specific phenotypic features including bifid uvula, hypertelorism, clef ... Full text Link to item Cite

Expanding the Clinical Spectrum of Mitochondrial Citrate Carrier (SLC25A1) Deficiency: Facial Dysmorphism in Siblings with Epileptic Encephalopathy and Combined D,L-2-Hydroxyglutaric Aciduria.

Chapter · 2015 Recessive mutations in SLC25A1 encoding mitochondrial citrate carrier cause a rare inherited metabolic disorder, combined D,L-2-hydroxyglutaric aciduria (D,L-2-HGA), characterized by epileptic encephalopathy, respiratory insufficiency, developmental arrest ... Full text Link to item Cite

Jaffe-Campanacci syndrome, revisited: detailed clinical and molecular analyses determine whether patients have neurofibromatosis type 1, coincidental manifestations, or a distinct disorder.

Journal Article Genet Med · June 2014 PURPOSE: "Jaffe-Campanacci syndrome" describes the complex of multiple nonossifying fibromas of the long bones, mandibular giant cell lesions, and café-au-lait macules in individuals without neurofibromas. We sought to determine whether Jaffe-Campanacci sy ... Full text Link to item Cite

The utility of the traditional medical genetics diagnostic evaluation in the context of next-generation sequencing for undiagnosed genetic disorders.

Journal Article Genet Med · February 2014 PURPOSE: The purpose of this study was to assess the diagnostic yield of the traditional, comprehensive clinical evaluation and targeted genetic testing, within a general genetics clinic. These data are critically needed to develop clinically and economica ... Full text Link to item Cite

Cytogenetic and Clinical Characterization of Three Cases of 17p13.3 Microduplication Involving PAFAH1B (LIS1)

Conference CYTOGENETIC AND GENOME RESEARCH · January 1, 2014 Link to item Cite

Novel FOXF1 mutations in sporadic and familial cases of alveolar capillary dysplasia with misaligned pulmonary veins imply a role for its DNA binding domain.

Journal Article Hum Mutat · June 2013 Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare and lethal developmental disorder of the lung defined by a constellation of characteristic histopathological features. Nonpulmonary anomalies involving organs of gastroin ... Full text Link to item Cite

Deficiency in SLC25A1, encoding the mitochondrial citrate carrier, causes combined D-2- and L-2-hydroxyglutaric aciduria.

Journal Article Am J Hum Genet · April 4, 2013 The Krebs cycle is of fundamental importance for the generation of the energetic and molecular needs of both prokaryotic and eukaryotic cells. Both enantiomers of metabolite 2-hydroxyglutarate are directly linked to this pivotal biochemical pathway and are ... Full text Link to item Cite

A 137-kb deletion within the Potocki-Shaffer syndrome interval on chromosome 11p11.2 associated with developmental delay and hypotonia.

Journal Article Am J Med Genet A · January 2013 Potocki-Shaffer syndrome (PSS) is a rare disorder caused by haploinsufficiency of genes located on the proximal short arm of chromosome 11 (11p11.2p12). Classic features include biparietal foramina, multiple exostoses, profound hypotonia, dysmorphic featur ... Full text Link to item Cite

Subtelomeric deletion of chromosome 10p15.3: clinical findings and molecular cytogenetic characterization.

Journal Article Am J Med Genet A · September 2012 We describe 19 unrelated individuals with submicroscopic deletions involving 10p15.3 characterized by chromosomal microarray (CMA). Interestingly, to our knowledge, only two individuals with isolated, submicroscopic 10p15.3 deletion have been reported to d ... Full text Link to item Cite

Clinical application of exome sequencing in undiagnosed genetic conditions.

Journal Article J Med Genet · June 2012 BACKGROUND: There is considerable interest in the use of next-generation sequencing to help diagnose unidentified genetic conditions, but it is difficult to predict the success rate in a clinical setting that includes patients with a broad range of phenoty ... Full text Link to item Cite

Further clinical and molecular delineation of the 15q24 microdeletion syndrome.

Journal Article J Med Genet · February 2012 BACKGROUND: Chromosome 15q24 microdeletion syndrome is a rare genomic disorder characterised by intellectual disability, growth retardation, unusual facial morphology and other anomalies. To date, 20 patients have been reported; 18 have had detailed breakp ... Full text Link to item Cite

Hereditary hemorrhagic telangiectasia: two distinct ENG deletions in one family.

Journal Article Clin Genet · November 2010 Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by aberrant vascular development. Mutations in endoglin (ENG) or activin A receptor type II-like 1 (ACVRL1) account for around 90% of HHT patients, 10% of those are ... Full text Link to item Cite

Mutations in WDR62, encoding a centrosome-associated protein, cause microcephaly with simplified gyri and abnormal cortical architecture.

Journal Article Nat Genet · November 2010 Genes associated with human microcephaly, a condition characterized by a small brain, include critical regulators of proliferation, cell fate and DNA repair. We describe a syndrome of congenital microcephaly and diverse defects in cerebral cortical archite ... Full text Link to item Cite

A recurrent 16p12.1 microdeletion supports a two-hit model for severe developmental delay.

Journal Article Nat Genet · March 2010 We report the identification of a recurrent, 520-kb 16p12.1 microdeletion associated with childhood developmental delay. The microdeletion was detected in 20 of 11,873 cases compared with 2 of 8,540 controls (P = 0.0009, OR = 7.2) and replicated in a secon ... Full text Link to item Cite

Clinical and mutational spectrum of neurofibromatosis type 1-like syndrome.

Journal Article JAMA · November 18, 2009 CONTEXT: Autosomal dominant inactivating sprouty-related EVH1 domain-containing protein 1 (SPRED1) mutations have recently been described in individuals presenting mainly with café au lait macules (CALMs), axillary freckling, and macrocephaly. The extent o ... Full text Link to item Cite

Expanding the clinical phenotype of the 3q29 microdeletion syndrome and characterization of the reciprocal microduplication.

Journal Article Mol Cytogenet · April 28, 2008 BACKGROUND: Interstitial deletions of 3q29 have been recently described as a microdeletion syndrome mediated by nonallelic homologous recombination between low-copy repeats resulting in an ~1.6 Mb common-sized deletion. Given the molecular mechanism causin ... Full text Link to item Cite

Multifocal anaplastic astrocytoma in a patient with hereditary colorectal cancer, transcobalamin II deficiency, agenesis of the corpus callosum, mental retardation, and inherited PMS2 mutation.

Journal Article Neuro Oncol · February 2008 We describe the case of a patient with transcobalamin II deficiency, hypogammaglobulinemia, absent corpus callosum, and mental retardation who presented at an early age with colorectal cancer and multifocal anaplastic astrocytoma. He was found to have a po ... Full text Link to item Cite

Three successful pregnancies through dietary management of fructose-1,6-bisphosphatase deficiency.

Journal Article J Inherit Metab Dis · October 2007 Fructose-1,6-bisphosphatase (FBPase) deficiency (OMIM 229700) has been characterized as the cause of life-threatening hypoglycaemia and lactic acidaemia following prolonged fasting. The patient, an adult African-American woman, presented during the second ... Full text Link to item Cite

The discovery of microdeletion syndromes in the post-genomic era: review of the methodology and characterization of a new 1q41q42 microdeletion syndrome.

Journal Article Genet Med · September 2007 PURPOSE: The advent of molecular cytogenetic technologies has altered the means by which new microdeletion syndromes are identified. Whereas the cytogenetic basis of microdeletion syndromes has traditionally depended on the serendipitous ascertainment of a ... Full text Link to item Cite

Agalsidase-beta therapy for advanced Fabry disease: a randomized trial.

Journal Article Ann Intern Med · January 16, 2007 BACKGROUND: Fabry disease (alpha-galactosidase A deficiency) is a rare, X-linked lysosomal storage disorder that can cause early death from renal, cardiac, and cerebrovascular involvement. OBJECTIVE: To see whether agalsidase beta delays the onset of a com ... Full text Link to item Cite

Recombinant human acid [alpha]-glucosidase: major clinical benefits in infantile-onset Pompe disease.

Journal Article Neurology · January 9, 2007 BACKGROUND: Pompe disease is a progressive metabolic neuromuscular disorder resulting from deficiency of lysosomal acid alpha-glucosidase (GAA). Infantile-onset Pompe disease is characterized by cardiomyopathy, respiratory and skeletal muscle weakness, and ... Full text Link to item Cite

An audit of the impact of implementation of a stroke care pathway in an acute teaching hospital.

Journal Article Ir J Med Sci · 2007 BACKGROUND: In 2002, a survey of stroke management was conducted in our institution benchmarked against the UK National Stroke Audit 2002. The conclusion was that management of stroke patients lacked organised and specialised care. The introduction of a st ... Full text Link to item Cite

Polymicrogyria and deletion 22q11.2 syndrome: window to the etiology of a common cortical malformation.

Journal Article Am J Med Genet A · November 15, 2006 Several brain malformations have been described in rare patients with the deletion 22q11.2 syndrome (DEL22q11) including agenesis of the corpus callosum, pachygyria or polymicrogyria (PMG), cerebellar anomalies and meningomyelocele, with PMG reported most ... Full text Link to item Cite

Clinical experience with array CGH: case presentations from nine months of practice.

Journal Article Am J Med Genet A · October 1, 2006 A total of 124 individuals were tested in the initial 9 months that array CGH technology was offered to clinical genetics patients. In 11 of these patients array CGH identified a previously unsuspected diagnosis. A suspected diagnosis was confirmed in thre ... Full text Link to item Cite

Juvenile bilateral lens dislocation and glaucoma associated with a novel mutation in the fibrillin 1 gene.

Journal Article Mol Vis · August 28, 2006 PURPOSE: To describe the clinical, ocular, and genetic findings in multiple members of a family with early-onset and bilateral lens dislocation, clinical corneal guttae, and glaucoma. METHODS: All family members underwent complete physical and ophthalmic e ... Link to item Cite

Incontinentia pigmenti in a boy with XXY mosaicism detected by fluorescence in situ hybridization.

Journal Article J Am Acad Dermatol · July 2006 We report the case of a male infant with incontinentia pigmenti (MIM 308310) and low-grade XXY mosaicism. Fluorescence in situ hybridization may reveal the underlying genetic alteration in male patients with incontinentia pigmenti and a normal karyotype. ... Full text Link to item Cite

Pelger-Huët anomaly in a child with 1q42.3-44 deletion.

Journal Article Pediatr Blood Cancer · May 1, 2006 Congenital Pelger-Huët anomaly (PHA) is an autosomal dominant disorder characterized by hypolobulated neutrophils with coarse clumping of the nuclear chromatin. PHA has been recently linked to the gene encoding the lamin B receptor, located at chromosome 1 ... Full text Link to item Cite

New chromosome 11p15 epigenotypes identified in male monozygotic twins with Beckwith-Wiedemann syndrome.

Journal Article Cytogenet Genome Res · 2006 Beckwith-Wiedemann syndrome (BWS) is an overgrowth syndrome demonstrating heterogeneous molecular alterations of two imprinted domains on chromosome 11p15. The most common molecular alterations include loss of methylation at the proximal imprinting center, ... Full text Link to item Cite

Triploid mosaicism in a 45,X/69,XXY infant.

Journal Article Am J Med Genet A · October 1, 2005 We report on an infant referred for chromosome analysis during the neonatal period due to ambiguous genitalia. The genitalia appeared male with bilaterally palpable testes, penoscrotal hypospadias, chordee, and a bifid scrotum. Chromosome analysis and inte ... Full text Link to item Cite

Molecular and clinical analyses of Greig cephalopolysyndactyly and Pallister-Hall syndromes: robust phenotype prediction from the type and position of GLI3 mutations.

Journal Article Am J Hum Genet · April 2005 Mutations in the GLI3 zinc-finger transcription factor gene cause Greig cephalopolysyndactyly syndrome (GCPS) and Pallister-Hall syndrome (PHS), which are variable but distinct clinical entities. We hypothesized that GLI3 mutations that predict a truncated ... Full text Link to item Cite

Falls in an acute hospital and their relationship to restraint use.

Journal Article Ir J Med Sci · 2005 BACKGROUND: Patient falls are a common complication of hospitalisation. Use of restraints in patients who are perceived to be at risk for falling may lead to injury and even death. AIMS: To determine the frequency of falls and fall-related injuries and the ... Full text Link to item Cite

Diagnostic and treatment challenges of neuronopathic Gaucher disease: two cases with an intermediate phenotype.

Journal Article J Inherit Metab Dis · 2004 Gaucher disease (GD) is a lysosomal storage disorder with a broad, overlapping clinical spectrum. The presented two case reports highlight the clinical evaluation required in neuronopathic GD to assist with medical management and genetic counselling. ... Full text Link to item Cite

Microduplication 22q11.2, an emerging syndrome: clinical, cytogenetic, and molecular analysis of thirteen patients.

Journal Article Am J Hum Genet · November 2003 Chromosome 22, particularly band 22q11.2, is predisposed to rearrangements due to misalignments of low-copy repeats (LCRs). DiGeorge/velocardiofacial syndrome (DG/VCFS) is a common disorder resulting from microdeletion within the same band. Although both d ... Full text Link to item Cite

Characterization of novel 4 and 6 Mb LCR-mediated microduplications involving the 22q11.2 DiGeorge/velocardiofacial syndrome region.

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

Rare disorders of metabolism with elevated butyryl- and isobutyryl-carnitine detected by tandem mass spectrometry newborn screening.

Journal Article Pediatr Res · August 2003 Tandem mass spectrometry was adopted for newborn screening by North Carolina in April 1999. Since then, three infants with short-chain acyl-CoA dehydrogenase (SCAD) and one with isobutyryl-CoA dehydrogenase deficiency were detected on the basis of elevated ... Full text Link to item Cite

Pelger-Huet anomaly in a child with 1q42.3-44 deletion

Conference PEDIATRIC RESEARCH · April 1, 2003 Link to item Cite

Evaluation of 3-methylcrotonyl-CoA carboxylase deficiency detected by tandem mass spectrometry newborn screening.

Journal Article J Inherit Metab Dis · 2003 Since the addition of tandem mass spectrometry (MS/MS) to the North Carolina Newborn Screening Program, 20 infants with two consecutive elevated 3-hydroxyisovalerylcarnitine (C5OH) levels have been evaluated for evidence of inborn errors of metabolism asso ... Full text Link to item Cite

Cytogenetic and FISH analysis of an interstitial 1q42.3-q44 deletion.

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

Fibromyalgia: patient perspectives on symptoms, symptom management, and provider utilization.

Journal Article Clin Nurse Spec · January 2002 Two surveys of individuals with fibromyalgia were conducted to assess the frequency and prevalence of symptoms (N = 99) as well as healthcare providers, medications, and self-care activities used to manage one's fibromyalgia (N = 54). The pervasiveness of ... Full text Link to item Cite

Clinical heterogeneity in lymphoedema-distichiasis with FOXC2 truncating mutations.

Journal Article J Med Genet · November 2001 BACKGROUND: Hereditary lymphoedema-distichiasis (LD) is an autosomal dominant disorder that classically presents as lymphoedema of the limbs, with variable age of onset, and extra aberrant growth of eyelashes from the Meibomian gland (distichiasis). Other ... Full text Link to item Cite

Phenotypic heterogeneity in lymphedema-distichiasis with FOXC2 mutations.

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

Mosaicism for two de novo supernumerary markers derived from chromosomes 18 and 13.

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

Congenital diaphragmatic defects: An autopsy case series

Journal Article MODERN PATHOLOGY · January 1, 2001 Link to item Cite

Congenital diaphragmatic defects: An autopsy case series

Journal Article LABORATORY INVESTIGATION · January 1, 2001 Link to item Cite

Refinement of a locus on chromosome 16q24.3 for Lymphedema-Distichiasis.

Journal Article AMERICAN JOURNAL OF HUMAN GENETICS · October 1, 2000 Link to item Cite

A novel inherited syndrome of early lens dislocation

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · March 15, 1999 Link to item Cite

XY sex reversal and gonadal dysgenesis due to 9p24 monosomy.

Journal Article Am J Med Genet · December 19, 1997 We describe a case of XY sex reversal, gonadal dysgenesis, and gonadoblastoma in a patient with a deletion of 9p24 due to a familial translocation. The rearranged chromosome 9 was inherited from the father; the patient's karyotype was 46,XY,der(9)t(8;9) (p ... Link to item Cite

Cosmids map two incontinentia pigmenti type 1 (IP1) translocation breakpoints to a 180-kb region within a 1.2-Mb YAC contig.

Journal Article Genomics · July 15, 1996 Incontinentia pigmenti (IP) is an X-linked dominant disorder of neuroectodermal development. Based on the observation of six unrelated females with clinical features of nonfamilial IP with constitutional de novo reciprocal X;autosome translocations, a puta ... Full text Link to item Cite

Cytogenetic and molecular analysis of inv dup(15) chromosomes observed in two patients with autistic disorder and mental retardation.

Journal Article Am J Med Genet · January 11, 1996 A variety of distinct phenotypes has been associated with supernumerary inv dup(15) chromosomes. Although different cytogenetic rearrangements have been associated with distinguishable clinical syndromes, precise genotype-phenotype correlations have not be ... Full text Link to item Cite

Galactosaemia--a controversial disorder. Screening & outcome. Ireland 1972-1992.

Journal Article Ir Med J · 1996 We reviewed 20 years (from 1972 to 1992) of screening for galactosaemia in Ireland. We looked at a small group of 32 patients followed up in the same centre since diagnosis. 1.2 million babies have been screened with 55 cases of classical galactosaemia and ... 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

Unbalanced 5;16 translocation in a boy with papillary thyroid carcinoma.

Journal Article Am J Med Genet · February 1, 1994 This is the first reported case of an unbalanced chromosome rearrangement resulting in trisomy 5q35.5-->qter and monosomy 16p 13.3-->pter, in a boy with mental and growth retardation, minor anomalies, and a history of bilateral papillary thyroid carcinoma. ... Full text Link to item Cite

Nager acrofacial dysostosis.

Journal Article J Med Genet · September 1993 Full text Link to item Cite

Dinucleotide repeat polymorphism at the human erythropoietin receptor locus (EPOR) at 19p13.

Journal Article Hum Mol Genet · May 1993 Full text Link to item Cite

Irish perinatal society - Proceedings of scientific meeting held in Cork, March 20-22nd, 1992

Journal Article Irish Journal of Medical Science · January 1, 1993 Full text Cite

Irish paediatric association - Proceedings of meeting

Journal Article Irish Journal of Medical Science · July 1, 1992 Full text Cite

Blood cultures and antibiotic use in a neonatal intensive care unit.

Journal Article Ir J Med Sci · January 1992 A review of the duration of antibiotic courses in our Neonatal Intensive Care Unit (N.I.C.U.) has shown that in a significant number of cases there was non compliance with the antibiotic policy. An audit of neonatal sepsis and antibiotic usage over a six m ... Full text Link to item Cite

Mixed connective tissue disease with arterial thrombosis, antiphospholipid antibodies and heparin induced thrombocytopenia.

Journal Article J Rheumatol · November 1990 We report a patient with mixed connective tissue disease (MCTD) who presented with thrombosis of the right femoral artery in association with antiphospholipid antibodies (aPL). When treated surgically and with heparin prophylaxis, she developed heparin ind ... Link to item Cite

Irish society of gastroenterlogy - Proceedings of Winter Meeting, Belfast City Hospital, Friday 24th and Saturday 25th November, 1989

Journal Article Irish Journal of Medical Science · July 1, 1990 Full text Cite

Irish association for rheumatology & rehabilitation - Proceedings of annual general meeting, Friday 3rd November 1989, university college, Cork

Journal Article Irish Journal of Medical Science · January 1, 1990 Full text Cite

Irish Association For Rheumatology And Rehabilitation Annual General Meeting, Friday, Nov. 4Th At Beaumont Hospital - Proceedings of Meeting held on Friday, November 4th, 1988 at Beaumont Hospital, Dublin

Journal Article Irish Journal of Medical Science · May 1, 1989 Full text Cite