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.
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| 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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| Authors | Hugh Young Rienhoff Jr, 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 |
| Journal | American journal of medical genetics. Part A (Am J Med Genet A) Vol. 161A Issue 8 Pg. 2040-6 (Aug 2013) ISSN: 1552-4833 [Electronic] United States |
| PMID | 23824657 (Publication Type: Case Reports, Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't) |
| Copyright | Copyright © 2013 Wiley Periodicals, Inc. |
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