Through a genome-wide search using the genetic markers(RFLP genetic markers), the familial hypertrophic cardiomyopathy(FHCM) with an autosomal dominant mode of inheritance has been firstly detected to be genetically linked to chromosome 14q1. The subsequent studies have shown that the point mutations at the exons encoding for the head and head /rod junction of the cardiac beta myosin heavy chain(β-MHC) are the most frequent type of mutation in the FHCM families genetically implicated with a linkage to β-MHC, whereas the α/β-MHC hybrid gene and a large deletion at the 3' region of β-MHC gene were also rarely detected. With the other families genetically implicated with the chromosomes 1,11,15,16 and 18, FHCM also manifests locus heterogeneity, a phenomenon in which abnormalities at different genes are involved in different families. In addition, a korean FHCM family with 403Arg→Gln mutation of β-MHC gene has been previously found by an american research group.

For clinical diagnosis, echocardiography and electrocardiography were performed on the individual members of a korean FHCM family. The microsatellite markers(MYO-I,MYO-II) located in the β-MHC gene region were amplified by PCR(polymerase chain reaction) and the polymorphism was analyzed for the possible linkage to the phenotypic expression of FHCM. Independently, the same PCR products of the exons 13 and 23 were digested with the specific restriction enzymes for the presence of the most frequently reported point mutations of β-MHC gene (403 and 908 amino acid mutations). Single strand conformation polymorphism(SSCP) of the exon 13 and 23 of the β-MHC gene was also analyzed of the mobility shift expected if any point mutation is present at these two exons.

The inheritance pattern of HCM(hypertrophic cardiomyopathy) in the family is considered as autosomal dominant. In this family(KU 101), one of the microsatellite markers(MYO-II) indicated the possible cosegregation between the allele was also present in the 32-year-old brother of the proband, who reveals no clinical signs of the disease. The other microsatellite genetic marker(MYO-I) was uninformative, without giving the discriminating power to verify the linkage to β-MHC gene. In the analysis for two common mutations of β-MHC gene by PCR-RFLP and PCR-SSCP, no evidence was found for 403 and 908 amino acid mutations and any point mutation in the exons 13 and 23.

Based on the linkage analysis using microsatellite genetic markers, there was a possibility that the disease could be linked to an abnormality in the β-MHC gene of the chromosome 14q1.