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

Hugh Young Rienhoff, Chang Yeol Yeo, Rachel Morissette, Irina Khrebtukova, Jonathan Melnick, Shujun Luo, Nan Leng, Yeon Jin Kim, Gary Schroth, John Westwick, Hannes Vogel, Nazli Mcdonnell, Judith G. Hall, Malcolm Whitman

Research output: Contribution to journalArticlepeer-review

75 Scopus citations

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 languageEnglish
Pages (from-to)2040-2046
Number of pages7
JournalAmerican Journal of Medical Genetics, Part A
Volume161
Issue number8
DOIs
StatePublished - 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

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