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CLINICAL STUDIES

The cardiac ß-myosin heavy chain gene is not the predominant gene for hypertrophic cardiomyopathy in the Finnish population

Pertti Jääskeläinen, MS^*, Marja Soranta, MSc, Raija Miettinen, MSc^*, Laura Saarinen, MS^*, Jussi Pihlajamäki, MD^*, Karoliina Silvennoinen, MS^*, Tero Tikanoja, MD, Markku Laakso, MD^* and Johanna Kuusisto, MD^*

^* Department of Medicine, University of Kuopio, Kuopio, Finland
Division of Environmental Health, National Public Health Institute, Kuopio, Finland
Department of Pediatrics, University of Kuopio, Kuopio, Finland

Manuscript received April 15, 1998; revised manuscript received July 8, 1998, accepted July 29, 1998.

Address for correspondence: Dr. Johanna Kuusisto, MD, Department of Medicine, Kuopio University Hospital, P.O. Box 1777, 70210 Kuopio, Finland
johanna.kuusisto{at}kuh.fi

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 ß-myosin heavy chain (ß-MHC) and -tropomyosin (-TM) genes.

Background. Mutations in the ß-MHC and -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 ß-MHC gene and the nine exons of the -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 ß-MHC gene were performed in 16 familial HCM kindreds.

Results. A previously reported Arg719Trp (arginine converted to tryptophan in codon 719) mutation of the ß-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 ß-MHC gene was observed in 16 familial kindreds. A previously reported Asp175Asn (aspartic acid converted to asparagine in codon 175) mutation of the -TM gene was found in four probands and 16 relatives. Mutations in the ß-MHC and -TM genes accounted for 6% and 25% familial HCM cases and 3% and 11% of all cases, respectively.

Conclusions. Our results indicate that the ß-MHC gene is not the predominant gene for HCM in the Finnish population, whereas HCM caused by the Asp175Asn mutation of the -TM gene is more common than previously reported.

Abbreviations and Acronyms   -TM = alpha-tropomyosin   Arg719Trp = arginine converted to tryptophan in codon 719   Asn696Ser = asparagine converted to serine in codon 696   Asp175Asn = aspartic acid converted to asparagine in codon 175   ß-MHC = beta-myosin heavy chain   HCM = hypertrophic cardiomyopathy   PCR = polymerase chain reaction   SSCP = single strand conformation polymorphism

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