Conflict of interest: none.
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
Article first published online: 3 JUL 2013
Copyright © 2013 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part A
Volume 161, Issue 8, pages 2040–2046, August 2013
How to Cite
2013. 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. Am J Med Genet Part A. 161A:2040–2046., , , , , , , , , , , , , .
This paper is dedicated to the memory of Victor A. McKusick and to the vitality of Beatrice.
- Issue published online: 24 JUL 2013
- Article first published online: 3 JUL 2013
- Manuscript Accepted: 29 APR 2013
- Manuscript Received: 28 SEP 2012
- Intramural Research Program of the National Institutes of Health, National Institutes of Aging
- National Research Foundation of Korea. Grant Number: 20090-0076374
- transforming growth factor beta;
- Marfan syndrome;
- Loeys–Dietz syndrome;
- distal arthrogryposis;
- low muscle mass;
- bifid uvula;
- exome sequencing;
- de novo mutation;
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. © 2013 Wiley Periodicals, Inc.