A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2.
We report heterozygous mutations in the genes encoding either type I or type II transforming growth factor beta receptor in ten families with a newly described human phenotype that includes widespread perturbations in cardiovascular, craniofacial, neurocognitive and skeletal development. Despite evidence that receptors derived from selected mutated alleles cannot support TGFbeta signal propagation, cells derived from individuals heterozygous with respect to these mutations did not show altered kinetics of the acute phase response to administered ligand. Furthermore, tissues derived from affected individuals showed increased expression of both collagen and connective tissue growth factor, as well as nuclear enrichment of phosphorylated Smad2, indicative of increased TGFbeta signaling. These data definitively implicate perturbation of TGFbeta signaling in many common human phenotypes, including craniosynostosis, cleft palate, arterial aneurysms, congenital heart disease and mental retardation, and suggest that comprehensive mechanistic insight will require consideration of both primary and compensatory events.
Altmetric Attention Stats
Dimensions Citation Stats
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Syndrome
- Skull
- Sequence Homology, Amino Acid
- Receptors, Transforming Growth Factor beta
- Receptor, Transforming Growth Factor-beta Type II
- Receptor, Transforming Growth Factor-beta Type I
- Protein Serine-Threonine Kinases
- Phenotype
- Mutation
- Molecular Sequence Data
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Syndrome
- Skull
- Sequence Homology, Amino Acid
- Receptors, Transforming Growth Factor beta
- Receptor, Transforming Growth Factor-beta Type II
- Receptor, Transforming Growth Factor-beta Type I
- Protein Serine-Threonine Kinases
- Phenotype
- Mutation
- Molecular Sequence Data