Abstract
The transforming growth factor β (TGF-β) family of growth factors are key regulators of mammalian development and their dysregulation is implicated in human disease, notably, heritable vasculopathies including Marfan (MFS, OMIM #154700) and Loeys-Dietz syndromes (LDS, OMIM #609192). We described a syndrome presenting at birth with distal arthrogryposis, hypotonia, bifid uvula, a failure of normal post-natal muscle development but no evidence of vascular disease; some of these features overlap with MFS and LDS. A de novo mutation in TGFB3 was identified by exome sequencing. Several lines of evidence indicate the mutation is hypomorphic suggesting that decreased TGF-β signaling from a loss of TGFB3 activity is likely responsible for the clinical phenotype. This is the first example of a mutation in the coding portion of TGFB3 implicated in a clinical syndrome suggesting TGFB3 is essential for both human palatogenesis and normal muscle growth.
Original language | English |
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Pages (from-to) | 2040-2046 |
Number of pages | 7 |
Journal | American Journal of Medical Genetics, Part A |
Volume | 161 |
Issue number | 8 |
DOIs | |
State | Published - Aug 2013 |
Keywords
- Bifid uvula
- De novo mutation
- Distal arthrogryposis
- Exome sequencing
- Hyomyoplasia
- Loeys-Dietz syndrome
- Low muscle mass
- Marfan syndrome
- Transforming growth factor beta