A mutation in TGFB3 associated with a syndrome of low muscle mass, growth retardation, distal arthrogryposis and clinical features overlapping with marfan and loeys–dietz syndrome. Issue 8 (3rd July 2013)

• Record Type: Journal Article
• Authors: Rienhoff, Hugh Young; Yeo, Chang‐Yeol; Morissette, Rachel; Khrebtukova, Irina; Melnick, Jonathan; Luo, Shujun; Leng, Nan; Kim, Yeon‐Jin; Schroth, Gary; Westwick, John; Vogel, Hannes; McDonnell, Nazli; Hall, Judith G.; Whitman, Malcolm
• Is Part Of: American journal of medical genetics. Volume 161:Issue 8(2013:Aug.)
• Page Start: 2040
• Page End: 2046
• Publication Date: 2013-07-03
• Subjects: Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.36056
• Languages: English
• ISSNs: 1552-4825

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="ajmga36056-sec-0001" sec-type="section"> <p>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. © 2013 Wiley Periodicals, Inc.</p> </sec> </abstract>