Affiliation:
1. From the Familial Cardiomyopathy Registry Research Group.
Abstract
Background—
Mutations in the β-myosin heavy-chain (βMyHC) gene cause hypertrophic (HCM) and dilated (DCM) forms of cardiomyopathy. In failing human hearts, downregulation of αMyHC mRNA or protein has been correlated with systolic dysfunction. We hypothesized that mutations in αMyHC could also lead to pleiotropic cardiac phenotypes, including HCM and DCM.
Methods and Results—
A cohort of 434 subjects, 374 (134 affected, 214 unaffected, 26 unknown) belonging to 69 DCM families and 60 (29 affected, 30 unaffected, 1 unknown) in 21 HCM families, was screened for αMyHC gene (
MYH6
) mutations. Three heterozygous
MYH6
missense mutations were identified in DCM probands (P830L, A1004S, and E1457K; 4.3% of probands). A Q1065H mutation was detected in 1 of 21 HCM probands and was absent in 2 unaffected offspring. All
MYH6
mutations were distributed in highly conserved residues, were predicted to change the structure or chemical bonds of αMyHC, and were absent in at least 300 control chromosomes from an ethnically similar population. The DCM carrier phenotype was characterized by late onset, whereas the HCM phenotype was characterized by progression toward dilation, left ventricular dysfunction, and refractory heart failure.
Conclusions—
This study suggests that mutations in
MYH6
may cause a spectrum of phenotypes ranging from DCM to HCM.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Physiology (medical),Cardiology and Cardiovascular Medicine
Cited by
196 articles.
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