The cardiac beta-myosin heavy chain gene is not the predominant gene for hypertrophic cardiomyopathy in the Finnish population.
OBJECTIVE
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 beta-myosin heavy chain (beta-MHC) and alpha-tropomyosin (alpha-TM) genes.


BACKGROUND
Mutations in the beta-MHC and alpha-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 beta-MHC gene and the nine exons of the alpha-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 beta-MHC gene were performed in 16 familial HCM kindreds.


RESULTS
A previously reported Arg719Trp (arginine converted to tryptophan in codon 719) mutation of the beta-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 beta-MHC gene was observed in 16 familial kindreds. A previously reported Aspl75Asn (aspartic acid converted to asparagine in codon 175) mutation of the alpha-TM gene was found in four probands and 16 relatives. Mutations in the beta-MHC and alpha-TM genes accounted for 6% and 25% familial HCM cases and 3% and 11% of all cases, respectively.


CONCLUSIONS
Our results indicate that the beta-MHC gene is not the predominant gene for HCM in the Finnish population, whereas HCM caused by the Aspl75Asn mutation of the a-TM gene is more common than previously reported.
Jääskeläinen
P
P
Department of Medicine, University of Kuopio, Finland.
Soranta
M
M
Miettinen
R
R
Saarinen
L
L
Pihlajamäki
J
J
Silvennoinen
K
K
Tikanoja
T
T
Laakso
M
M
Kuusisto
J
J
D019943:Amino Acid Substitution; D001483:Base Sequence; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics*; D005260:Female; D005387:Finland; D008040:Genetic Linkage / Q000235:genetics; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics; D009206:Myocardium / Q000201:enzymology*; D018995:Myosin Heavy Chains / Q000235:genetics*; D010375:Pedigree; D014335:Tropomyosin / Q000235:genetics
D014335:Tropomyosin; D018995:Myosin Heavy Chains