Echocardiographic-determined septal morphology in Z-disc hypertrophic cardiomyopathy

Jeanne L. Theis, J. Martijn Bos, Virginia B. Bartleson, Melissa L. Will, Josepha Binder, Matteo Vatta, Jeffrey A. Towbin, Bernard J. Gersh, Steve R. Ommen, Michael J. Ackerman

Research output: Contribution to journalArticlepeer-review

72 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)896-902
Number of pages7
JournalBiochemical and Biophysical Research Communications
Issue number4
StatePublished - Dec 29 2006


  • Cardiomyopathy
  • Echocardiography
  • Genes
  • Hypertrophy
  • Septum
  • Z-disc

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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