权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Analysis of ankyrin gene mutations in hereditary spherocytosis

遗传性球形红细胞增多症锚蛋白基因突变分析

基本信息

批准号：
09672369
负责人：
IDEGUCHI Hirosho
金额：
$ 1.22万
依托单位：
Fukuoka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09672369/
关键词：
Hereditary spherocytosis Ankyrin Gene analysis アンキリン遺伝子変異

项目摘要

We analyzed all exons (exon 1 - exon 42) and promotor region of ankyrin gene in 36 Japanese patients with hereditary spherocytosis (HS). Genomic DNAs were extracted from peripheral blood leukocytes and PCR (polymerase chain reaction)-amplified DNA fragments were subjected to screen ankyrin mutations by non-RI SSCP (single strand conformation polymorphism) method. The DNA fragments showing abnormal SSCPs were analyzed by direct DNA sequencing. As the results, we found 19 ankyrin gene mutations : 2 nonsense mutations, 6 missense mutations, 1 deletional mutation (deletion of 8 bases in intron), 1 intronic base substitution, and 9 silent mutations. Two nonsense mutations (E886X : GAG - TAG ; K1140X : AAG - TAG) were novel mutations that have not been reported, and may be directly involved in ankyrin deficiency which result in reduced assembly of underlying cytoskeletal proteins. Although further investigation should be needed to clarify whether 6 missense mutations are the primary defects of HS or mere polymorphisms, it was a notable evidence that 3 patients were a homozygote of the missense mutation (I1075T : ATC - ACC). We showed ankyrin gene mutations are one of the cause of Japanese patients with HS and these incidence may be 10 - 20%.

我们分析了36例日本遗传性球形红细胞增多症（HS）患者锚蛋白基因的所有外显子（外显子1 -外显子42）和启动子区。从外周血白细胞中提取基因组DNA，PCR（polymerase chain reaction，聚合酶链反应）扩增DNA片段，采用非RI单链构象多态性（single strand conformation polymorphism，SSCP）方法检测锚蛋白基因突变。通过直接DNA测序分析显示异常SSCP的DNA片段。结果发现19个锚蛋白基因突变：无义突变2个，错义突变6个，缺失突变（内含子中8个碱基缺失）1个，内含子碱基替换1个，沉默突变9个。两个无义突变（E886 X：GAG-TAG; K1140 X：AAG-TAG）是尚未报道的新突变，并且可能直接涉及锚蛋白缺陷，其导致潜在的细胞骨架蛋白组装减少。尽管需要进一步研究以阐明6个错义突变是HS的主要缺陷还是仅仅是多态性，但3名患者是错义突变（I1075 T：ATC-ACC）的纯合子是一个值得注意的证据。我们发现锚蛋白基因突变是日本HS患者的原因之一，这些发生率可能为10 - 20%。