GENOTYPE-PHENOTYPE ANALYSIS IN 4 FAMILIES WITH MUTATIONS IN BETA-MYOSIN HEAVY-CHAIN GENE RESPONSIBLE FOR FAMILIAL HYPERTROPHIC CARDIOMYOPATHY

Familial hypertrophic cardiomyopathy is a genetically heterogeneous di sease in which one of the most frequently implicated gene is the gene encoding the beta-myosin heavy chain. To date, more than 40 distinct m utations have been found within this gene. In order to progress on the determination of genotype-phenotype relationship, we have screened th e beta-myosin heavy chain gene for mutations in 18 probands from unrel ated families. We identified the mutation implicated in the disease in four families. Two of them, the Glu930 codon deletion and the Ile263T hr mutation, are reported here for the first time. The two other mutat ions are the Arg723Cys mutation, that was previously described in a pr oband as a de novo mutation, and the Arg719Trp mutation. A poor progno sis was associated with the Glu930codon deletion (mean maximal wall th ickness (MWT) = 19.5 mm +/- 5) and the Arg719Trp mutation (mean MWT = 15.3 mm +/- 7), whereas a good prognosis was associated with the Arg72 3Cys mutation (mean MWT = 20.1 mm +/- 7). The combination of clinical and genetic characteristics of each family member suggests that progno sis is related neither to the degree of left ventricular wall thicknes s nor to a change in the net electrical charge of the protein. Additio nal family studies are needed to confirm these findings and to contrib ute to stratify the prognosis according to the mutation involved. Hum Mutat 12:385-392, 1998. (C) 1998 Wiley-Liss, Inc.