Objectives. The aim of the study was to screen 36 unrelated patients with hypertrophic cardiomyopathy (HCM; 16 familial and 20 sporadic cases) from a genetically homogeneous area in eastern Finland for variants in the cardiac β-myosin heavy chain (β-MHC) and α-tropomyosin (α-TM) genes.
Background. Mutations in the β-MHC and α-TM genes have been reported to be responsible for 30% to 40% and less than 5% of familial HCM cases, respectively. However, most genetic studies have included patients from tertiary care centers and are subject to referral bias.
Methods. Exons 3-26 and 40 of the β-MHC gene and the nine exons of the α-TM gene were screened with the PCR–SSCP (polymerase chain reaction–single strand conformation polymorphism) method. Linkage analyses between familial HCM locus and two intragenic polymorphic markers (MYO I and MYO II) of the β-MHC gene were performed in 16 familial HCM kindreds.
Results. A previously reported Arg719Trp (arginine converted to tryptophan in codon 719) mutation of the β-MHC gene was found in one proband and two relatives. In addition, a novel Asn696Ser (asparagine converted to serine in codon 696) substitution was found in one HCM patient. No linkage between familial HCM and the β-MHC gene was observed in 16 familial kindreds. A previously reported Asp175Asn (aspartic acid converted to asparagine in codon 175) mutation of the α-TM gene was found in four probands and 16 relatives. Mutations in the β-MHC and α-TM genes accounted for 6% and 25% familial HCM cases and 3% and 11% of all cases, respectively.
Conclusions. Our results indicate that the β-MHC gene is not the predominant gene for HCM in the Finnish population, whereas HCM caused by the Asp175Asn mutation of the α-TM gene is more common than previously reported.