New Locus for Autosomal Dominant Mitral Valve Prolapse on Chromosome 13: Clinical Insights From Genetic Studies

  title={New Locus for Autosomal Dominant Mitral Valve Prolapse on Chromosome 13: Clinical Insights From Genetic Studies},
  author={Francesca Nesta and Maire Leyne and Chaim Yosefy and Charles Simpson and Daisy Dai and Jane E. Marshall and Judy W Hung and Susan A. Slaugenhaupt and Robert A. Levine},
Background—Mitral valve prolapse (MVP) is a common disorder associated with mitral regurgitation, endocarditis, heart failure, and sudden death. To date, 2 MVP loci have been described, but the defective genes have yet to be discovered. In the present study, we analyzed a large family segregating MVP, and identified a new locus, MMVP3. This study and others have enabled us to explore mitral valve morphological variations of currently uncertain clinical significance. Methods and Results… 

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The genetics of mitral valve prolapse

The report warrants the need for further genetically based studies on this common, albeit not fully understood, clinical entity.

Genetic Complexity of Mitral Valve Prolapse Revealed by Clinical and Genetic Evaluation of a Large Family.

While a contributory role for PTPRJ and FLYWCH1 in this family cannot be excluded, the study results underscores the difficulties involved in uncovering the genomic contribution to MVP, even in apparently Mendelian families.

Genetic mechanisms of mitral valve prolapse

Three-dimensional echocardiographic studies demonstrating the saddle shape of the mitral valve have increased the specificity of diagnosis and provided a strong phenotypic basis for genetic studies.

Genetic association analyses highlight biological pathways underlying mitral valve prolapse

The first risk loci for MVP are identified and new mechanisms involved in mitral valve regurgitation are suggested, including tensin 1, a focal adhesion protein involved in cytoskeleton organization, which is shown during valve morphogenesis.

Genetic background of mitral valve prolapse.

The present review aims to illustrate the updated genetic background of MVP, which involves a heterogeneous group of patients with different expressions and according to the phenotype can be further divided into fibroelastic deficiency and myxomatous disease, frequently associated with familiar clusters.

Early Expression of Mitral Valve Prolapse in the Framingham Offspring: Phenotypic Spectrum

The prodromal form did not meet diagnostic criteria but resembled fully diagnostic MVP with regards to D, T and JH (all p > 0.05); they were similar morphology and MSD may represent early expressions of MVP and additional studies are warranted to elucidate the natural history of these phenotypes.

Mutations in DCHS1 Cause Mitral Valve Prolapse

A missense mutation in the DCHS1 gene, the human homologue of the Drosophila cell polarity gene dachsous (ds), that segregates with MVP in the family is reported, supporting these processes as aetiological underpinnings for the disease.

New insights into mitral valve dystrophy: a Filamin-A genotype–phenotype and outcome study

FLNA-MVD has unique features with both MVP and paradoxical restricted motion in diastole, sub-valvular mitral apparatus impairment and polyvalvULAR lesions in males, and conveys a substantial lifetime risk of valve surgery in men.

Filamin-A-Related Myxomatous Mitral Valve Dystrophy: Genetic, Echocardiographic and Functional Aspects

The genetic, echocardiographic and functional aspects of the filamin-A-related myxomatous mitral valve dystrophy are described.

Epidemiology and Pathophysiology of Mitral Valve Prolapse: New Insights Into Disease Progression, Genetics, and Molecular Basis

The current knowledge of the diagnosis, epidemiology, prognosis, and genetic mechanisms underlying the pathogenesis and progression of mitral valve prolapse are summarized.



A locus for autosomal dominant mitral valve prolapse on chromosome 11p15.4.

The results of a genome scan are described and it is shown that a locus for MVP maps to chromosome 11p15, and a new MVP locus, MMVP2, is confirmed, which confirms the genetic heterogeneity of this disorder.

Mapping of a first locus for autosomal dominant myxomatous mitral-valve prolapse to chromosome 16p11.2-p12.1.

By systematic echocardiographic screening of the first-degree relatives of 17 patients who underwent mitral-valve repair, four pedigrees showing an autosomal dominant inheritance of the trait are identified, demonstrating the genetic heterogeneity of the disease.

Inheritance of mitral valve prolapse: effect of age and sex on gene expression.

The familial prevalence of prolapse was similar whether or not the proband had characteristic symptoms, auscultatory abnormalities, electrocardiographic findings, thoracic bony abnormalities, or coexistent heart disease.

Association of mitral valve prolapse and systemic abnormalities of connective tissue. A phenotypic continuum.

Until subclassification based on refined clinical, genetic, and laboratory investigations is possible, patients evaluated for the possible diagnosis of a heritable disorder of connective tissue are best seen as having an "overlap" heritable connective-tissue disorder.

Mapping of X-linked myxomatous valvular dystrophy to chromosome Xq28.

The genetic analysis of a large family in which XMVD is associated with a mild hemophilia A is described, in which the coagulation factor VIII gene position in Xq28 provided a starting point for the genetic study, conducted by use of polymorphic markers.

Genetic segregation analysis of familial mitral valve prolapse shows no linkage to fibrillar collagen genes.

Three pedigrees were identified in which mitral valve prolapse seemed to be inherited as a mendelian autosomal dominant trait, evidence against the disease being generally the result of mutations of the genes encoding the major fibrillar collagens.

Familial hypertrophic cardiomyopathy is a genetically heterogeneous disease.

We demonstrate that familial hypertrophic cardiomyopathy (FHC), an autosomal dominant disorder of heart muscle, is a genetically heterogeneous disease. The locus responsible for FHC in members of one

Mitral valve prolapse in the general population: the benign nature of echocardiographic features in the Framingham Heart Study.

Echocardiographically documented mitral-valve prolapse. Long-term follow-up of 237 patients.

Most patients with echocardiographic evidence of mitral-valve prolapse have a benign course, but subsets at high risk for the development of progressive mitral regurgitation, sudden death, cerebral embolic events, or infective endocarditis can be identified by echOCardiography.

Identification of high-risk and low-risk subgroups of patients with mitral-valve prolapse.

It is concluded that in a selected population of patients with mitral-valve prolapse, those with the classic form (leaflet thickening and redundancy) are at higher risk than those without these features for the infectious and hemodynamic complications ofMitral- Valvular disorder, but not for stroke.