Carrier Dectection and Prenatal Diagnosis of Hemophilia Ain Korean Populations Using PCR Analysis of DNA Polymorphismin St14 VNTR Locus

Choi, Young Min; Hwang, Do Yeong; Choe, Jin; Jun, Jong Kwan; Suh, Chang Suk; Kim, Seok Hyun; Kim, Jung Gu; Moon, Shin Yong; Lee, Jin Yong; Kim, Eun Joo

Abstract

At present, because of enormous variety of mutations in hemophilia A, carrier detection and prenatal diagnosis by DNA analysis has been relied almost always on indirect detection using linkage analysis of DNA polymorphisms withim or near to the factor VIII gene. However, there is marked ethnic variation in the incidence of heterozygosity for a given DNA polymorphism. So it is very important to find out which DNA polymorphism pattern is useful in Korean families with hemophilia A for carrier detection and prenatal diagnosis. To identify the usefulness of DNA polymorphism in St14 VNTR locus for carrier detection and prenatal diagnosis of hemophilia A in Korean populations, we have analysed the DNA polymorphism in St14 VNTR locus in 80 Korean families with hemophilia A using polymerase chain reaction. We could identify 14 alleles in subjects studied, which ranges from 620 bp to 2830 bp. Expected heterozygosity rate, calculated from the allele frequencies, was 78.7%, and observed heterozygosity rate was 71.3% (57/80). Carrier detection was performed in 43 women from families informative with St14 VNTR : Seventeen women were diagnosed as non-carriers, 11 women as carriers. And 15 women were suspected to be carriers since they were from families of sporadic cases of hemophilia A. And prenatal diagnosis was done in 4 pregnant carrier women : noe fetus proved to be normal males, two fetuses to be normal females, and one to be a carrier. And five pregnant women, suspected to be carrier since they were from families of sporadic cases of hemophilia A, underwent prenatal diagnosis : One fetus was diagnosed as a normal mali, one as a normal female, two as possible carriers, and one as a possible affeted mali, whom the analysis of factor VIII level in fetal blood by cordocentesis revealed to be affected by hemophilia A. These data indicate that PCR-based analysis of St14 VNTR is very useful for the carrier detection and prenatal diagnosis of hemophilia A in Korea.