Analysis of genotype and phenotype in fukuyama congenital muscular dystrophy.
OBJECTIVE
To do a genetic study of clinically diagnosed Fukuyama congenital muscular dystrophy (FCMD) by means of haplotype analysis, and to study the correlation of genotype and phenotype in FCMD.


METHODS
Six closest available informative markers for each of the mapped FCMD genes were tested in 100 Japanese families with at least one affected patient.


RESULTS
Seventy-seven percent of FCMD-bearing chromosomes had an ancestral founder haplotype(138-192-147-183) and 10 chromosomes had a second founder haplotype(130-201-157-183). Thirty-five(69%) typical, and 20(77%) mild, while 5(19%) severe cases were homozygous for the founder haplotype. On the contrary, 13(25%) typical, 5(19%) mild, and 15(65%) severe cases were heterozygous. Eight of 10 that were heterozygous for the second founder haplotype had the severe phenotypes. Two typical cases with severe brain and ophthalmologic anomalies were also heterozygous for the second founder haplotype.


CONCLUSIONS
Homozygosity was associated with the typical and mild phenotypes, while compound heterozygosity was related to the severe phenotype. The value of the second founder haplotype in predicting disease severity was suggested.
Wang
Z
Z
Department of Pediatrics, Shanghai Xinhua Hospital, Shanghai Second Medical University, Shanghai, 200092 P. R. China. wangzhp@online.sh.cn
Kayoko
S
S
Makiko
O
O
D005838:Genotype; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D009136:Muscular Dystrophies / Q000235:genetics*; D010641:Phenotype