Echocardiographic-determined septal morphology in Z-disc hypertrophic cardiomyopathy

Biochem Biophys Res Commun. 2006 Dec 29;351(4):896-902. doi: 10.1016/j.bbrc.2006.10.119. Epub 2006 Nov 9.


Hypertrophic cardiomyopathy (HCM) can be classified into at least four major anatomic subsets based upon the septal contour, and the location and extent of hypertrophy: reverse curvature-, sigmoidal-, apical-, and neutral contour-HCM. Here, we sought to identify genetic determinants for sigmoidal-HCM and hypothesized that Z-disc-HCM may be associated preferentially with a sigmoidal phenotype. Utilizing PCR, DHPLC, and direct DNA sequencing, we performed mutational analysis of five genes encoding cardiomyopathy-associated Z-disc proteins. The study cohort consisted of 239 unrelated patients with HCM previously determined to be negative for mutations in the eight genes associated with myofilament-HCM. Blinded to the Z-disc genotype status, the septal contour was graded qualitatively using standard transthoracic echocardiography. Thirteen of the 239 patients (5.4%) had one of 13 distinct HCM-associated Z-disc mutations involving residues highly conserved across species and absent in 600 reference alleles: LDB3 (6), ACTN2 (3), TCAP (1), CSRP3 (1), and VCL (2). For this subset with Z-disc-associated HCM, the septal contour was sigmoidal in 11 (85%) and apical in 2 (15%). While Z-disc-HCM is uncommon, it is equal in prevalence to thin filament-HCM. In contrast to myofilament-HCM, Z-disc-HCM is associated preferentially with sigmoidal morphology.

MeSH terms

  • Actin Cytoskeleton / genetics
  • Adult
  • Alleles
  • Cardiomyopathy, Hypertrophic / diagnostic imaging
  • Cardiomyopathy, Hypertrophic / genetics*
  • Cardiomyopathy, Hypertrophic / pathology*
  • DNA Mutational Analysis
  • Echocardiography
  • Female
  • Heart Septum / diagnostic imaging
  • Heart Septum / pathology*
  • Humans
  • Male
  • Microfilament Proteins / genetics*
  • Middle Aged
  • Mutation


  • Microfilament Proteins