Echocardiographic-determined septal morphology in Z-disc hypertrophic cardiomyopathy.
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.
Theis
Jeanne L
JL
Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.
Bos
J Martijn
JM
Bartleson
Virginia B
VB
Will
Melissa L
ML
Binder
Josepha
J
Vatta
Matteo
M
Towbin
Jeffrey A
JA
Gersh
Bernard J
BJ
Ommen
Steve R
SR
Ackerman
Michael J
MJ
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
D008840:Microfilament Proteins