| Co-Investigator(Kenkyū-buntansha) |
KANZAKI Akio Medicine, Kawasaki Medical School, Assistant Professor, 医学部, 講師 (40148698)
SUGIHARA Takashi Medicine, Kawasaki Medical School, Assistant Professor, 医学部, 講師 (60140505)
YAMADA Osamu Medicine, Kawasaki Medical School, Associate Professor, 医学部, 助教授 (50104790)
KAKU Mayumi Medicine, Kawasaki Medical School, Research Associate, 医学部, 助手 (20319940)
WADA Hideho Medicine, Kawasaki Medical School, Assistant Professor, 医学部, 講師 (70191830)
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| Research Abstract |
(I) Phenotypic features of red cell membrane disorders in Japan :
We have studied 118 cases from 100 kindred of hereditary spherocytosis (HS), which is the most common red cell membrane disorder in Japan. Among them, 48 cases of 30 kindred were HS of autosomal dominant (AD) transmission, and 70 cases of 70 kindred were those of non-AD type. Clinical features were nearly identical in the two groups. Phenotypically, band 3 (B3) deficiency was observed in one-fourth of HS patients, and protein 4.2 (P4.2) in one-third. There was nearly no cases with ankyrin (ANK) deficiency. In one-third of HS, no detectable deficiency of membrane proteins was observed.
(II) Genotypic features of HS :
12 mutations pathognomonic for HS were detected in the B3 gene (EPB3) : 4 frameshift mutations and 8 missense mutations, in addition to 7 gene polymorphisms. In the ANK gene (ANK1), there were 16 pathognomonic mutations (4 nonsense mutations, 8 frameshift mutations, and 4 abnormal splicings) with 17 gene polymorphisms (2 missense and 15 silent mutations). In the P4.2 gene (ELB42), 3 critical missense mutations (P4.2 Nippon, P4.2 Shiga, and P4.2 Komatsu) were detected.
(III) Methylation status as a control mechanism of gene expression :
The state of methylation was studied at the 5-C pG-3' sites in the promoter region of the B3 gene (EPB3), the P4.2 gene (ELB42), and β-spectrin gene (SPTB). These sites were highly methylation-sensitive. SPTB was always unmethylated, and EPB3 was substantially methylated.
However, the state of methylation in ELB42 was switched from "unmethylated" in very early erythroid progenitors to "methylated" in mature erythroid cells, concomitant to the expression of mRNA of ELB42 and of P4.2 protein.
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