title: Echocardiographic-determined septal morphology in Z-disc hypertrophic cardiomyopathy.
abstract: 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.
authors.affiliation: Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.
authors.forename: Jeanne L
authors.initials: JL
authors.lastname: Theis
authors.forename: J Martijn
authors.initials: JM
authors.lastname: Bos
authors.forename: Virginia B
authors.initials: VB
authors.lastname: Bartleson
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Will
authors.forename: Josepha
authors.initials: J
authors.lastname: Binder
authors.forename: Matteo
authors.initials: M
authors.lastname: Vatta
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Towbin
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: Gersh
authors.forename: Steve R
authors.initials: SR
authors.lastname: Ommen
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Ackerman
mesh_terms: D008841:Actin Cytoskeleton / Q000235:genetics; D000328:Adult; D000483:Alleles; D002312:Cardiomyopathy, Hypertrophic / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology*; D004252:DNA Mutational Analysis; D004452:Echocardiography; D005260:Female; D006346:Heart Septum / Q000000981:diagnostic imaging / Q000473:pathology*; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation
chemical_list: D008840:Microfilament Proteins