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

作者：Rienhoff Hugh Young Jr^*; 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

来源：American Journal of Medical Genetics, Part A, 2013, 161(8): 2040-2046.

DOI：10.1002/ajmg.a.36056

• transforming growth factor beta
• Marfan syndrome
• Loeys-Dietz syndrome
• distal arthrogryposis
• low muscle mass
• bifid uvula
• exome sequencing
• de novo mutation
• hyomyoplasia

The transforming growth factor beta (TGF-beta) 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-beta 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.

• 出版日期2013-8