한국인 듀센형 근디스트로피 가계에서의 보인지 진단을 위한 DNA 제한효소 단편 장다형에 관한 연구

Abstract

Background : Duchenne muscular dystrophy (DMD) is a severe X-linked recessive disease and cloned probes recognize genetic variations of restriction endonuclease sites (restriction fragment length polymorphisms (RFLPs)). These RFLPs may be inherited together with nearby genes and can be useful for the diagnosis of carrier. Methods : We obtaind peripheral blood from unrelated individuals for the analysis of 51-78 X-chromsomes in number and from 27 members of seven DMD families. DNA was isolated from white blood cells and RFLP analysis were performed using PERT series of probes (87-1, 87-8, 87-15), which detects a BstNM, TaqI and XmnI RFLP, respectively. Allelic frequencies and heterozygosity rates were calculated to assess the diagnostic usefulness and linkage analysis was performed to observe the informativeness in DMD families. Results : The allele frequencies of three intragenic pERT probes were 0.49/0.51, 0.69/0.31 and 0.49/0.51 among 87-1/BstNI, 87´S// TagI, and 87-15/XmnI, respectively. Among the three polymorphic sites, calculated and observed heterozygosity rates of 87-1/BstNI and 87-15/Xmnl were higher than those of 87-8/Tags. The total informa￢tiveness in seven DMD families could be as high as 86% in our patient population. Conclusions : By using three intragenic pERT probes, different genotypes could be determined and the heterozygosity was high enough to be effective in carrier diagnosis. The combined use of linkage analysis based on pERT RFLPs and deletion analysis by cDNA or rapid multiplex polymerase chain reaction can provide a improved method for carrier detection and prenatal diagnosis of DMD