K. Yamauchitakihara et al., CLINICAL IMPLICATIONS OF HYPERTROPHIC CARDIOMYOPATHY ASSOCIATED WITH MUTATIONS IN THE ALPHA-TROPOMYOSIN GENE, HEART, 76(1), 1996, pp. 63-65
Objective-The disease-bearing genes for hypertrophic cardiomyopathy (H
CM) in HCM families have been identified as the beta-myosin heavy chai
n, alpha-tropomyosin, and cardiac troponin T genes. Three HCM kindreds
with three distinct point mutations in the alpha-tropomyosin gene had
extensive clinical evaluations.Design and results-Single-strand confo
rmation polymorphism gel analysis of polymerase chain reaction amplifi
ed products was used to capture each of the nine exons from the alpha-
tropomyosin gene to identify mutations in 60 familial HCM patients. Tw
o missense mutations in exon 2 (Ala63Val and Lys70Thr) and one missens
e mutation in exon 5 (Asp175Asn) were found in three unrelated HCM kin
dreds. These kindreds were the subject of clinical, electrocardiograph
ic and echocardiographic studies. The morphological appearance of HCM
was similar in the three kindreds. All the patients had severe hypertr
ophy of the left ventricle with asymmetrical septal hypertrophy during
the early stage of the disease, which gradually progressed to dilatat
ion of the left ventricle. Moreover, these kindreds showed similar dis
ease penetrance, age of onset, and incidence of premature sudden death
. The disease in these kindreds was severe and resulted in frequent su
dden deaths. Conclusions-Among Japanese patients with familial HCM mut
ations in the alpha-tropomyosin gene are not as rare as reported, acco
unting for about 5% of all cases. These mutations are characterised by
hypertrophy of the left ventricle which then progresses to dilatation
and a high incidence of sudden or disease-related death.