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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.

Authors
  • Rienhoff, Hugh Young Jr1
  • 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
  • 1 Children's Hospital Oakland Research Institute, Oakland, CA 94070, USA. [email protected]
Type
Published Article
Journal
American Journal of Medical Genetics Part A
Publisher
Wiley (John Wiley & Sons)
Publication Date
Aug 01, 2013
Volume
161A
Issue
8
Pages
2040–2046
Identifiers
DOI: 10.1002/ajmg.a.36056
PMID: 23824657
Source
Medline
Keywords
License
Unknown

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.

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