IDENTIFICATION OF 2 NOVEL DELETION MUTATIONS IN GLUCOSE-6-PHOSPHATE-DEHYDROGENASE GENE CAUSING HEMOLYTIC-ANEMIA

Among over 50 distinct mutations causing glucose-6-phosphate dehydroge nase (G6PD) deficiency, only two deletion mutations have so far been r eported. Using nonradioisotopic single-strand conformation polymorphis m analysis, we found two additional deletion mutations in two Japanese G6PD-deficient patients with nonspherocytic hemolytic anemia, Case no . 1 had a 3-nucleotide deletion in exon 6 predicting a deletion of a s erine at amino acid 188 or 189, which caused a class 1 variant GGPD Ts ukui, Case no, 2 had a 3-nucleotide deletion in exon 5 predicting a de letion of a lysine at residue 95, which caused a class 2 variant G6PD Urayasu. The 188th serine, which might be deleted in G6PD Tsukui, is l ocated close to the putative G6P binding site, The 188th serine is als o involved in the amino acid substitution in G6PD Mediterranean, but t he kinetics of these two variants are totally different. The residue w ith an amino acid deletion in G6PD Urayasu was distant from the substr ate binding sites and was located in a region with low sequence homolo gy among species. The different properties of variants having mutation s in exons 5 and 6 suggest that these two exons code distinct function al domains of the enzyme. (C) 1995 by The American Society of Hematolo gy.