title: New locus for autosomal dominant mitral valve prolapse on chromosome 13: clinical insights from genetic studies.
abstract: 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.
  
  
  RESULTS
  Echocardiograms and blood samples were obtained from 43 individuals who were classified by the extent and pattern of displacement. Genotypic analyses were performed with polymorphic microsatellite markers. Evidence of linkage was obtained on chromosome 13q31.3-q32.1, with a peak nonparametric linkage score of 18.41 (P<0.0007). Multipoint parametric analysis gave a logarithm of odds score of 3.17 at marker D13S132. Of the 6 related individuals with mitral valve morphologies not meeting diagnostic criteria but resembling fully developed forms, 5 carried all or part of the haplotype linked to MVP.
  
  
  CONCLUSIONS
  The mapping of a new MVP locus to chromosome 13 confirms the observed genetic heterogeneity and represents an important step toward gene identification. Furthermore, the genetic analysis provides clinical lessons with regard to previously nondiagnostic morphologies. In the familial context, these may represent early expression in gene carriers. Early recognition of gene carriers could potentially enhance the clinical evaluation of patients at risk of full expression, with the ultimate aim of developing interventions to reduce progression.
authors.affiliation: Department of Medicine, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Francesca
authors.initials: F
authors.lastname: Nesta
authors.forename: Maire
authors.initials: M
authors.lastname: Leyne
authors.forename: Chaim
authors.initials: C
authors.lastname: Yosefy
authors.forename: Charles
authors.initials: C
authors.lastname: Simpson
authors.forename: Daisy
authors.initials: D
authors.lastname: Dai
authors.forename: Jane E
authors.initials: JE
authors.lastname: Marshall
authors.forename: Judy
authors.initials: J
authors.lastname: Hung
authors.forename: Susan A
authors.initials: SA
authors.lastname: Slaugenhaupt
authors.forename: Robert A
authors.initials: RA
authors.lastname: Levine
mesh_terms: D000328:Adult; D000368:Aged; D002874:Chromosome Mapping; D002882:Chromosomes, Human, Pair 13; D004452:Echocardiography; D005260:Female; D005799:Genes, Dominant; D018740:Genetic Heterogeneity; D008040:Genetic Linkage; D006801:Humans; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D008945:Mitral Valve Prolapse / Q000000981:diagnostic imaging / Q000235:genetics*; D010375:Pedigree