摘要
目的探讨胰岛素受体基因突变在严重胰岛素抵抗综合征中的发病机制。方法采用PCR对一临床拟诊A型胰岛素抵抗综合征患者胰岛素受体的22个外显子进行扩增并直接测序,测得突变所在外显子后,将其一级亲属的相应外显子进行扩增并直接测序。结果先证者及其父亲均为胰岛素受体第20号外显子R1174W杂合错义突变,另发现先证者胰岛素受体3处外显子纯合同义突变及6处内含子变异。胰岛素受体第20号外显子R1174W杂合子突变引起胰岛素受体β亚基酪氨酸激酶活性下降和自身磷酸化缺陷。结论胰岛素受体第20号外显子R1174W杂合子突变是导致该家系先证者及其父亲严重胰岛素抵抗的主要原因,不排除环境因素及其它基因突变的合并存在造成临床表型差异的可能。
Objective To investigate the role of insulin receptor gene mutation in the pathogenesis of severe insulin resistance syndrome. Methods PCR and DNA direct sequencing of PCR products were applied to examine the variants in all the 22 exons of insulin receptor(IR) gene in a patient diagnosed as type A insulin resistance syndrome, as well as related exons in her first degree relatives. Results A previously reported heterozygous missense mutation of R1174W (CGG→TGG) in exon 20 was identified in both the proband and her father, while her mother was heterozygous for a silent mutation of P1178(CCG/CCA). Another 3 silent mutations and 6 intronic polymorphisms were also detected in the proband. The heterozygous missense mutation of R1174W in exon 20 induces the decrease in tyrosine kinase activity of insulin receptor β subunit and the deficiency of its autophosphorylation. Conclusions The heterozygous mutation of R1174W in exon 20 plays a major role in severe insulin resistance syndrome of the proband and her father. In addition to insulin receptor gene, environmental factors and other genes may play roles in the phenotypic variation of insulin resistance syndrome.
出处
《中华内分泌代谢杂志》
CAS
CSCD
北大核心
2005年第3期237-239,共3页
Chinese Journal of Endocrinology and Metabolism
基金
2000年度广东省科委重点攻关项目(2KM05001S)
