| Research Abstract |
(I)Genotypic and phenotypic studies on red cell membrane disorders in the Japanese population : In the second year (2001 - 2002), studies on red cell membrane disorders were further extended following the first year of this project (2000 - 2001). The subjects were 64 cases from 31 independent kindred ; 16 cases of 13 kindred in hereditary spherocytosis(HS). Three cases of two kindred in hereditary elliptocytosis (HE). Two cases of two kindred in total deficiency of protein 4.2(P4.2), two cases of one kindred of hereditary stomatocylosis, and other cases under investigation. Total number of cases studied has reached to 1078 cases of 636 kindred since 1974.
(II)Gene analysis in Japanese HS : We identified 12.mutations of band 3(B3) gene (EPB3) ; three frameshift mutations one splicing mutation, and eight missense mutations, 19 mutations of ankyrin (Ank) gene CANK. D : nine frameshift mutations, four nonsense mutations, and six splicing mutations, and three missense mutations of protein 4.2 (P4.2) gene (ELB42). Except for two mutations in EPB3, all the mutations were specific for the Japanese population.
(III)State of methylation of the red cell membrane protein genes : mfmn. P49, FT Three red cell membrane protein genes were selected for this study : B3(EPB3), P4.2CELB42), and B -spectrin (SFTB). In SPTB, many CpG sites were present as one of house-keeping genes and absolutely unmethylated. In ELB42, CpG sites were unmethylated in the erythroid precursors in the established cell line CUT-7), although they were methylated in mature erythroid cells. In EPB3, sites E and G were substantially hypomethylated in spite of reasonably methylated CpG sites at other locations.
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