So far only mutations in the filamin A gene (FLNA) have been identified as causing familial mitral valve prolapse (MVP). Previous studies have linked dysregulation of the transforming growth factor beta (TGF-β) cytokine family to MVP. We investigated whether mutations in the TGF-β receptors genes type I (TGFBR1) and II (TGFBR2) underlie isolated familial MVP cases. Eight families with isolated familial MVP were evaluated clinically and genetically. Ventricular arrhythmias were present in five of the eight families and sudden cardiac death occurred in six patients. Tissue obtained during mitral valve surgery or autopsy was available for histological examination in six cases; all demonstrated myxomatous degeneration. A previously described FLNA missense mutation (p.G288R) was identified in one large family, but no mutations were discovered in TGFBR1 or TGFBR2. An FLNA missense mutation was identified in one family but we found no TGFBR1 or TGFBR2 mutations. Our results suggest that TGFBR1 and TGFBR2 mutations do not play a major role in isolated myxomatous valve dystrophy. Screening for FLNA mutations is recommended in familial myxomatous valvular dystrophy, particularly if X-linked inheritance is suspected.

Familial mitral valve prolapse, Filamin, Myxomatous degeneration, Transforming growth factor beta
dx.doi.org/10.1002/ajmg.a.36211, hdl.handle.net/1765/61955
American Journal of Medical Genetics. Part A
Department of Clinical Genetics

Aalberts, J.J.J, van Tintelen, J.P, Oomen, T, Bergman, J.E.H, Halley, D.J.J, Jongbloed, J.D.H, … van den Berg, M.P. (2014). Screening of TGFBR1, TGFBR2, and FLNA in familial mitral valve prolapse. American Journal of Medical Genetics. Part A, 164(1), 113–119. doi:10.1002/ajmg.a.36211