先天性antithrombin III(AT III)欠乏症家系におけるAT III遺伝子のDNA解析

DNA samples from white blood cells of 9 patients and 10 healthy members in 3 Japanese kindreds (Family Mo, Mi and Tu) with congenital antithrombin III (AT III) deficiency, and of 48 normal Japanese individuals were analysed by Southern blotting method using AT III cDNA probe PA62.
Restriction fragment length polymorphism (RFLP) by uses of Pst I and PA62 demonstrated + allele in 50%, - allele in 50%, F allele in 59% and S allele in 41% of 96 alleles from 48 normal Japanese individuals, indicating that the frequencies of RFLP in Japanese are almost the same as those in other races reported before. This suggests that DNA analysis on Japanese families with congenital AT III deficiency was possible using RFLP of AT III gene because of high frequencies of RFLP in normal Japanese.
All patients in 3 kindreds with congenital AT III deficiency had a -/+ genotype, indicating that complete deletion of one allele of AT III gene can be neglected. No abnormal DNA fragments were observed by Southern blot analysis of genomic DNAs from the patients in the 3 kindreds digested with various restriction enzymes (Bam HI, Eco RI, Hind III, Bgl II, Bcl I, Kpn I, Pvu II, Sac I, Taq I and Xba I). This suggests that AT III deficiency in our 3 kindreds is not caused by major structural alterations such as partial deletion, rearrangement and duplication, small deletion, insertion or limited nucleotide substitution in the AT III gene. In addition, it was suggested by analysis of polymorphism of AT III gene in the members of Family Mo and Mi that abnormal AT III gene existed on -, F allele in these families.