THE CARDIAC BETA-MYOSIN HEAVY-CHAIN GENE IS NOT THE PREDOMINANT GENE FOR HYPERTROPHIC CARDIOMYOPATHY IN THE FINNISH POPULATION

Objectives. The aim of the study was to screen 36 unrelated patients w ith hypertrophic cardiomyopathy (HCM; 16 familial and 20 sporadic case s) from a genetically homogeneous area in eastern Finland for variants in the cardiac beta-myosin heavy chain (beta-MHC) and alpha-tropomyos in (alpha-TM) genes. Background. Mutations in the beta-MHC and alpha-T M genes have been reported to be responsible for 30% to 40% and less t han 5% of familial HCM cases, respectively. However, most genetic stud ies have included patients from tertiary care centers and are subject to referral bias. Methods. Exons 3-26 and 40 of the beta-MHC gene and the nine exons of the alpha-TM gene were screened with the PCR-SSCP (p olymerase chain reaction-single strand conformation polymorphism) meth od. Linkage analyses between familial HCM locus and two intragenic pol ymorphic markers (MYO I and MYO II) of the beta-MHC gene were performe d in 16 familial HCM kindreds. Results. A previously reported Arg719Tr p (arginine converted to tryptophan in codon 719) mutation of the beta -MHC gene was found in one proband and two relatives. In addition, a n ovel Asn696Ser (asparagine converted to serine in codon 696) substitut ion was found in one HCM patient. No linkage between familial HCM and the beta-MHC gene was observed in 16 familial kindreds. A previously r eported Asp175Asn (aspartic acid converted to asparagine in codon 175) mutation of the alpha-TM gene was found in four probands and 16 relat ives. Mutations in the beta-MHC and alpha-TM genes accounted for 6% an d 25% familial HCM cases and 3% and 11% of all cases, respectively. Co nclusions. Our results indicate that the beta-MBC gene is not the pred ominant gene for HCM in the Finnish population, whereas HCM caused by the Asp175Asn mutation of the alpha-TM gene is more common than previo usly reported. (J Am Cell Cardiol 1998;32:1709-16) (C) 1998 by the Ame rican College of Cardiology.