Molecular Genetics of Hereditary Red Cell Membrane Disorders

本研究项目在1996.1学年取得的成果如下：3带异常：(1)遗传性球胞症冲绳家族中，冲绳等位基因存在3个突变(“(1)”K56E: AAG*GAG，“（2)”P854L: CCG*CTG，“(3)”G714R: GGG*AGG），另一个等位基因存在1个突变（G130R: GGA*AGA）。本研究项目在1996学年取得的成果如下：复合突变导致蛋白4.2完全缺失，带3部分缺失。采用分子生物学、生化分析和电子显微镜等方法研究了红色的表型特征。(2)牛完全3级缺乏症是这一类的第一例。该性状有明显的酸中毒、生长迟缓和显著的微球增多症。蛋白4.1 （4.1 (-)Madrid）完全缺失时受损细胞骨架网络的分子电镜研究：正如法国研究小组（Jean Delaunay教授）先前报道的那样，由于起始密码子（AUG）突变，4.1蛋白在4.1 (-)Madrid中完全缺失。电镜分析表明，由于蛋白4.1的完全缺失，细胞骨架网络明显扭曲和破坏。其他结果：发现了其他新的红细胞膜疾病，特别是蛋白4.2和遗传性球形红细胞增多症。明确了这些病例的表型和基因型。

The follwing results were obtained under this research project in the academic year of 1996.1.Band 3 abnormalities :(1)In the Okinawa family with hereditary spherocytosis, three mutations ("(1)"K56E : AAG*GAG, "(2)"P854L : CCG*CTG, "(3)"G714R : GGG*AGG) were detected on the allele Okinawa, in addition to a mutation (G130R : GGA*AGA) in the other allele. The following results were obtained under this research project in the academic year of 1996. The compound mutations induced a total absence of protein 4.2 with a partial deficiency of band 3. Phenotypic characteristics in the red were studied by molecular bioligy, biochemical analysis and electron microscopy.(2)Complete band 3 deficiency in cattle was reported as the first case in this category. The trait suffered from marked acidosis, retarded growth, and striking microspherocytosis.2.Molecular electron microscopic studies on the impaired cytoskeletal network in complete deficiency of protein 4.1 (4.1 (-) Madrid) :Protein 4.1 was totally missing in the 4.1 (-) Madrid due to the mutation at the initiation codon (AUG), as previously reported by the French group (Prof. Jean Delaunay). It was proven that the cytoskeletal network was markedly distorted and disrupted by the total absence of protein 4.1 by electron microscopic analysis.Other results :Other novel cases of red cell membrane disorders were detected, especially on protein 4.2, and hereditary spherocytosis. The phenotypes and genotypes were clarified on these cases.