[Genetic heterogeneity of hypertrophic cardiomyopathy in Japanese].

Familial hypertrophic cardiomyopathy (FHCM) is thought to be caused by missense mutations in cardiac beta-myosin heavy chain (beta-MHC) gene in 30-40% of affected Caucasian individuals. On the other hand, it has been reported that Japanese FHCM is closely linked to DNA marker PALB on chromosome 18q by linkage analysis. Therefore, in order to elucidate the etiological significance of missense mutations in beta-MHC gene in Japanese HCM patients, we have investigated the sequence variation in exon 3 to 25 of beta-MHC gene from 16 multiplex FHCM kindreds and 28 sporadic patients by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) method. In this study we demonstrated one missense mutation (codon741: GlyGGG-->ArgAGG) in only one kindred among 16 multiplex Japanese kindreds with FHCM. Two synonymous mutations (codon715: TryTAC-->TryTAT, codon 989: IleATT-->IleATC) are demonstrated in another kindred. The same mutation in codon 989 is also detected in one sporadic patient. Furthermore, we performed linkage study with two DNA markers (F13B on chromosome 1q, D11S916: AMF185yal on chromosome 11p-q) which are recently reported to be linked with FHCM. Three and four families showed statistically negative linkage with F13B and D11S916 (AMF185yal), respectively. These results suggest that several responsible genes for HCM may exist in Japanese and principal responsible gene for Japanese HCM is different from it for Caucasian HCM.