| 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)
WADA Hideho Medicine, Kawasaki Medical School, Assistant Professor, 医学部, 講師 (70191830)
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| Research Abstract |
(I) Characterization of the phenotypes of red cell membrane disorders :
During our research term for 2 years (1998 and 1999), we have studied 175 cases from 135 kindred of congenital red cell membrane disorders including 118 patients from 100 kindred of hereditary spherocytosis (HS). Clinical phenotypes were determined by clinical hematology studies, membrane protein biochemistry, molecular electron microscopy, and biophysical analyses.
(II) Genotypic analyses in HS :
On the band 3 gene (EPB3), 12 pathognomonic mutations were detected : 4 frameshift mutations and 8 missense mutations with 7 gene polymorphisms. On the ankyrin gene (ANK1), 16 pathognomonic mutations (4 nonsense mutations, 8 frameshift mutations, and 4 abnormal splicings) with 17 gene polymorphisms (2 missense mutations and 15 silent mutations) were identified. On the protein 4.2 gene (ELB42), 3 pathognomonic missense mutations had been found.
(III) Sequential expression of membrane proteins during erythroid differentiation :
In human red cell membranes, spectrins and band 3 were expressed in early erythroid precursors, protein 4.1 followed, and protein 4.2 was finally expressed at the very late erythroblasts sequentially.
(IV) The state of methylation of 5'-CpG-3' sites of the promoter regions of EPB3, SPTB, and ELB42
In SPTB, all of the 5'-CpG-3' sites were totally unmethylated, in contrast to nearly total methylation in EPB3. In ELB42, methylation was absent in very early erythroblasts, although all the sites were nearly completely methylated in mature erythroid cells.
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