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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 AMERICAN JOURNAL OF MEDICAL GENETICS PART A Rienhoff, H. Y., Yeo, C., Morissette, R., Khrebtukova, I., Melnick, J., Luo, S., Leng, N., Kim, Y., Schroth, G., Westwick, J., Vogel, H., McDonnell, N., Hall, J. G., Whitman, M. 2013; 161 (8): 2040-2046

Abstract

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

View details for DOI 10.1002/ajmg.a.36056

View details for Web of Science ID 000327789600031

View details for PubMedCentralID PMC3885154