POPULATION SCREENING OF LACTATE-DEHYDROGENASE DEFICIENCIES IN FUKUOKAPREFECTURE IN JAPAN AND MOLECULAR CHARACTERIZATION OF 3 INDEPENDENT MUTATIONS IN THE LACTATE DEHYDROGENASE-B(H) GENE

Screening for lactate dehydrogenase (LDH) subunit deficiencies was per formed on 2880 blood samples from healthy individuals in the Fukuoka P refecture in Japan by means of electrophoresis. The frequencies of het erozygotes with either LDH-A or LDH-B deficiency were found to be 0.10 4% at each locus. These estimated frequencies of either LDH-A or LDH-B deficiencies were slightly lower than, but not significantly differen t from, those found previously in Shizuoka Prefecture. The genetic mut ations in individuals heterozygous for LDH-B deficiency were analyzed by the polymerase chain reaction and DNA conformation polymorphism. Ab normal migration patterns were observed in individuals heterozygous fo r LDH-B deficiency. Subsequent sequence determination of the mutant al leles revealed three novel mutations: an eight-base duplication in exo n 3, a four-base duplication in exon 4, and a one-base deletion in exo n 7 of the LDH-B gene. These three mutations result in frameshift tran slation and premature termination. In addition, the mutations resultin g in the duplication of eight or four nucleotides appear to cause a de crease in the levels of LDH-B mRNA.