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Optimized Protocol for the Extraction of Proteins from the Human Mitral Valve
Published on: June 14, 2017
Screening of TGFBR1, TGFBR2, and FLNA in familial mitral valve prolapse
Jan J J Aalberts1, J Peter van Tintelen, Toon Oomen
1Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Abstract:
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.
Insights
Genetic analysis revealed that mutations in transforming growth factor beta receptors (TGFBR1 and TGFBR2) are not a common cause of familial mitral valve prolapse (MVP). Filamin A (FLNA) gene mutations are implicated in familial MVP.
Area of Science:
- Cardiovascular Genetics
- Molecular Cardiology
- Genetic Etiology of Valve Disease
Background:
- Familial mitral valve prolapse (MVP) is primarily linked to mutations in the filamin A gene (FLNA).
- Dysregulation of the transforming growth factor beta (TGF-β) pathway has been associated with MVP, suggesting potential roles for its receptors.
Purpose of the Study:
- To investigate the role of mutations in TGF-β receptor type I (TGFBR1) and type II (TGFBR2) genes in isolated familial MVP.
- To determine if TGFBR1 or TGFBR2 mutations contribute to the genetic basis of familial myxomatous valve dystrophy.
Main Methods:
- Clinical and genetic evaluation of eight families with isolated familial MVP.
- Histological examination of cardiac tissue from six patients to assess myxomatous degeneration.
- Genetic sequencing of TGFBR1 and TGFBR2 genes in affected individuals.
Main Results:
- A previously identified FLNA missense mutation (p.G288R) was found in one family.
- No mutations in TGFBR1 or TGFBR2 were identified in any of the evaluated families.
- Histological analysis confirmed myxomatous degeneration in all examined tissue samples.
Conclusions:
- TGFBR1 and TGFBR2 mutations do not appear to be a significant cause of isolated familial myxomatous valve dystrophy.
- FLNA gene mutations are implicated in familial myxomatous valvular dystrophy, especially in cases with suspected X-linked inheritance.
- Further investigation into FLNA mutations is warranted for familial MVP cases.
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