title: Novel correlations between the genotype and the phenotype of hypertrophic and dilated cardiomyopathy: results from the German Competence Network Heart Failure.
abstract: OBJECTIVE
  Hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) can both be due to mutations in the genes encoding β-myosin heavy chain (MYH7) or cardiac myosin-binding protein C (MYBPC3). The aim of the present study was to determine the prevalence and spectrum of mutations in both genes in German HCM and DCM patients and to establish novel genotype-to-phenotype correlations.
  
  
  RESULTS
  Coding exons and intron flanks of the two genes MYH7 and MYBPC3 of 236 patients with HCM and 652 patients with DCM were sequenced by conventional and array-based means. Clinical records were established following standard protocols. Mutations were detected in 41 and 11% of the patients with HCM and DCM, respectively. Differences were observed in the frequency of splice site and frame-shift mutations in the gene MYBPC3, which occurred more frequently (P< 0.02, P< 0.001, respectively) in HCM than in DCM, suggesting that cardiac myosin-binding protein C haploinsufficiency predisposes to hypertrophy rather than to dilation. Additional novel genotype-to-phenotype correlations were found in HCM, among these a link between MYBPC3 mutations and a particularly large thickness of the interventricular septum (P= 0.04 vs. carriers of a mutation in MYH7). Interestingly, this correlation and a link between MYH7 mutations and a higher degree of mitral valve regurgitation held true for both HCM and DCM, indicating that the gene affected by a mutation may determine the magnitude of structural and functional alterations in both HCM and DCM.
  
  
  CONCLUSIONS
  A large clinical-genetic study has unravelled novel genotype-to-phenotype correlations in HCM and DCM which warrant future investigation of both the underlying mechanisms and the prognostic use.
authors.affiliation: Universität Witten/Herdecke, Institut für Herz-Kreislaufforschung, Otto-Hahn-Str. 15, 44227 Dortmund, Germany. waldmueller@herz-kreislaufforschung.de
authors.forename: Stephan
authors.initials: S
authors.lastname: Waldmüller
authors.forename: Jeanette
authors.initials: J
authors.lastname: Erdmann
authors.forename: Priska
authors.initials: P
authors.lastname: Binner
authors.forename: Götz
authors.initials: G
authors.lastname: Gelbrich
authors.forename: Sabine
authors.initials: S
authors.lastname: Pankuweit
authors.forename: Christian
authors.initials: C
authors.lastname: Geier
authors.forename: Bernd
authors.initials: B
authors.lastname: Timmermann
authors.forename: Janine
authors.initials: J
authors.lastname: Haremza
authors.forename: Andreas
authors.initials: A
authors.lastname: Perrot
authors.forename: Steffen
authors.initials: S
authors.lastname: Scheer
authors.forename: Rolf
authors.initials: R
authors.lastname: Wachter
authors.forename: Norbert
authors.initials: N
authors.lastname: Schulze-Waltrup
authors.forename: Anastassia
authors.initials: A
authors.lastname: Dermintzoglou
authors.forename: Jost
authors.initials: J
authors.lastname: Schönberger
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Zeh
authors.forename: Beate
authors.initials: B
authors.lastname: Jurmann
authors.forename: Turgut
authors.initials: T
authors.lastname: Brodherr
authors.forename: Jan
authors.initials: J
authors.lastname: Börgel
authors.forename: Martin
authors.initials: M
authors.lastname: Farr
authors.forename: Hendrik
authors.initials: H
authors.lastname: Milting
authors.forename: Wulf
authors.initials: W
authors.lastname: Blankenfeldt
authors.forename: Richard
authors.initials: R
authors.lastname: Reinhardt
authors.forename: Cemil
authors.initials: C
authors.lastname: Özcelik
authors.forename: Karl-Josef
authors.initials: KJ
authors.lastname: Osterziel
authors.forename: Markus
authors.initials: M
authors.lastname: Loeffler
authors.forename: Bernhard
authors.initials: B
authors.lastname: Maisch
authors.forename: Vera
authors.initials: V
authors.lastname: Regitz-Zagrosek
authors.forename: Heribert
authors.initials: H
authors.lastname: Schunkert
authors.forename: Thomas
authors.initials: T
authors.lastname: Scheffold
mesh_terms: D002311:Cardiomyopathy, Dilated / Q000453:epidemiology / Q000235:genetics*; D002312:Cardiomyopathy, Hypertrophic / Q000453:epidemiology / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D009154:Mutation; D010641:Phenotype