BACKGROUND: Mutations in the beta-myosin heavy-chain (betaMyHC) gene cause 
hypertrophic (HCM) and dilated (DCM) forms of cardiomyopathy. In failing human 
hearts, downregulation of alphaMyHC mRNA or protein has been correlated with 
systolic dysfunction. We hypothesized that mutations in alphaMyHC 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 alphaMyHC 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 alphaMyHC, 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.