摘要
Background： Facioscapulohumeral muscular dystrophy （FSHD）, a common autosomal dominant muscular disorder, is caused by contraction of the D4Z4 repeats on 4q35. The complicated genotype-phenotype correlation among different ethnic population remains a controversial subject. We aimed to refine this correlation in order to provide new information for genetic counseling. Methods： Here, a cohort of[36 Chinese families including 178 affected individuals and 137 unaffected members were investigated. Genetic analyses were pertbrmed using the pl 3E-11, 4qA and 4qB probes after pulsed field gel electrophoresis separation and southern blotting. A I 0-grade FSHD clinical severity scale was adopted for clinical assessment. The genotype-phenotype correlation was established by linear regression analyses. Results： We observed a roughly inversed correlation between the short EcoRl fragment size and age-corrected clinical severity score in 154 symptomatic patients （P 〈 0.05）. Compared to male patients, a significant higher proportion of females in both asymptomatic carriers and severe patients showed larger variation in the size of short EcoRI fragment. A high incidence （ 19/42, 45.2%） ofasymptomatic （or minimally affected） carriers was found in familial members. Conclusions： Although the number of D4Z4 repeats is known as one of the critical influences on genotype-phenotype correlation, a rnajority ofphenotypic spectrum was still incompatible with their heterozygous contraction of the D4Z4 repeat, especial in female cases. Our resuhs suggest that there are multi-factors synergistically modulating the phenotypic expression.
Background： Facioscapulohumeral muscular dystrophy （FSHD）, a common autosomal dominant muscular disorder, is caused by contraction of the D4Z4 repeats on 4q35. The complicated genotype-phenotype correlation among different ethnic population remains a controversial subject. We aimed to refine this correlation in order to provide new information for genetic counseling. Methods： Here, a cohort of[36 Chinese families including 178 affected individuals and 137 unaffected members were investigated. Genetic analyses were pertbrmed using the pl 3E-11, 4qA and 4qB probes after pulsed field gel electrophoresis separation and southern blotting. A I 0-grade FSHD clinical severity scale was adopted for clinical assessment. The genotype-phenotype correlation was established by linear regression analyses. Results： We observed a roughly inversed correlation between the short EcoRl fragment size and age-corrected clinical severity score in 154 symptomatic patients （P 〈 0.05）. Compared to male patients, a significant higher proportion of females in both asymptomatic carriers and severe patients showed larger variation in the size of short EcoRI fragment. A high incidence （ 19/42, 45.2%） ofasymptomatic （or minimally affected） carriers was found in familial members. Conclusions： Although the number of D4Z4 repeats is known as one of the critical influences on genotype-phenotype correlation, a rnajority ofphenotypic spectrum was still incompatible with their heterozygous contraction of the D4Z4 repeat, especial in female cases. Our resuhs suggest that there are multi-factors synergistically modulating the phenotypic expression.
