FOUNDER-HAPLOTYPE ANALYSIS IN FUKUYAMA-TYPE CONGENITAL MUSCULAR-DYSTROPHY (FCMD)

Fukuyama-type congenital muscular dystrophy (FCMD) is an autosomal rec essive, severe muscular dystrophy associated with brain anomalies. Aft er our initial mapping of the FCMD locus to 9q31-33, we performed link age disequilibrium analysis, which led us to suspect that the FCMD gen e lay within a region of less than 100 kb containing D9S2107. In the p resent study, we developed two new microsatellites (D9S2170 and D9S217 1) in close vicinity to D9S2107 and examined haplotypes of FCMD chromo somes by using four markers (cen-D9S2105-D9S2170-D9S2171-D9S2107-tel). As 82% of the FCMD chromosomes that we examined shared the founder ha plotype (138-192-147-183) and 94% of the FCMD patients in our panel ca rried founder haplotypes on one or both chromosomes, the data supporte d the hypothesis of a single founder of this disease in the Japanese p opulation. Eight haplotypes different from the founder's were observed in FCMD chromosomes, indicating that eight different FCMD mutations i n addition to the founder's have occurred in Japan. Moreover, we have detected several historical recombinations that have disrupted the fou nder haplotype at D9S2105 or D9S2170 and conclude that the FCMD gene i s probably located just centromeric to D9S2170.