Cellular biochemistry and electron microscopy in hereditary red cell membrane disorders

近两年（1995-1997年）的研究结果如下：1.遗传性球形红细胞增多症：（1）锚蛋白/血影蛋白异常在日本的发生率似乎远低于西方国家。(2)在50例HS患者中检测到带3基因的4个突变，在50例正常人和20例HS患者中检测到锚蛋白基因的11个多态性和1个突变。(3)HS的一个性状携带8p.2的染色体异常。条带4.2：（1）检测到两个新的条带4.2完全缺失的突变：（1）等位基因4.2 Komatsu（523 GAT * 达特）和等位基因4.2滋贺（317 CGC *TGC）。(2)通过电子显微镜观察到在完全条带4.2缺陷中的膜内颗粒和细胞骨架网络上存在显著的紊乱。(3)条带4.2被证明与血影蛋白直接结合。(4)从生物化学和分子生物学的角度对4.2带双联体Nagano的致病机理进行了研究.带3：（1）完全带3缺乏是世界首例。(2)在带3福冈纯合子的表型特征。(3)带3和血型糖蛋白A的联合缺乏被认为是一种膜糖蛋白异常。(4)在带3 Okinawa中检测到4个新的带3基因突变.红细胞膜的形态发生：红细胞分化过程中膜蛋白的表达是以血影蛋白、血型糖蛋白和带3开始的，然后是带4.1和锚蛋白，到分化末期以带4.2的表达完成.遗传性椭圆形红细胞增多症：（1）β-血影蛋白Natoya基因缺陷。(2)在完全条带4.1缺陷（等位基因4.1（-）马德里）的红细胞中，通过电子显微镜观察到膜内颗粒和细胞骨架网络的明显紊乱。

The following results were obtained for the recent two years (1995-1997) :1. Hereditary spherocytosis :(1) Ankyrin/spectrin anomalies appeared to be much less frequent in Japan, compared with those in Western countries.(2) Four mutations in the band 3 gene in 50 HS patients and 11 polymorphism and one mutation in the ankyrin gene were detected in 50 normal subjects and 20 HS patients.(3) A trait of HS carried a chromosomal anomaly of 8p.2. Band 4.2 :(1) Two novel mutations with complete band 4.2 deficiency were detected : (1) allele 4.2 Komatsu (523GAT*TAT) and allele 4.2 Shiga (317CGC*TGC).(2) Marked derangements were observed on the intramembrane particles and the cytoskeletal network in the complete band 4.2 deficiencies by electron microscopy.(3) Band 4.2 was proved to have a direct binding to spectrins.(4) The pathogenesis of band 4.2 doublet Nagano was studied by biochemistry and molecular biology.3. Band 3 :(1) Complete band 3 deficiency was described as the first case in the world.(2) Phenotypic characteristics were reported in homozygotes of band 3 Fukuoka.(3) A combined deficiency of band 3 and glycophorin A was found as a membrane glycoprotein anomaly.(4) Four novel mutations of band 3 gene were detected in band 3 Okinawa.4. Morphogenesis of red cell membranes :It was shown that the expression of membrane proteins in erythroid differentiation was initiated in spectrins, glycophorins and band 3, followed by band 4.1 and ankyrin, and completed by the expression of band 4.2 at the last stage of the differentiation.5. Hereditary elliptocytosis :(1) The gene defect was identified in beta-spectrin Natoya.(2) Marked derangement of the intramembrane particles and the cytoskeletal network was observed by electron microscopy in red cells of the complete band 4.1 deficiency (allele 4.1 (-) Madrid).