A型胰岛素抵抗综合征1个家系的胰岛素受体基因新发突变分析  

Analysis of novel mutations in the insulin receptor gene of a family with type A insulin resistance syndrome

作　　者：李一君[1] 杨国庆[2] 臧丽[1] 裴育[1] 陈康[1] 杜锦[1] 吕朝晖[1] Li Yijun;Yang Guoqing;Zang Li;Pei Yu;Chen Kang;Du Jin;Lyu Zhaohui(Department of Endocrinology,the First Medical Center of Chinese PLA General Hospital,Beijing 100039,China;Department of Endocrinology,Hainan Hospital of Chinese PLA General Hospital,Sanya 572013,China)

机构地区：[1]解放军总医院第一医学中心内分泌科,北京100039 [2]解放军总医院海南医院内分泌科,三亚572013

出　　处：《中华内科杂志》2025年第3期239-243,共5页Chinese Journal of Internal Medicine

基　　金：北京市自然科学基金(7222168);国家重点研发计划(2016YFC1305200)。

摘　　要：探讨严重胰岛素抵抗综合征患者及其家系胰岛素受体基因(INSR)突变的遗传机制。对解放军总医院第一医学中心内分泌科收治的1例临床拟诊A型胰岛素抵抗综合征的患者进行INSR基因Sanger测序,并对其一级亲属相应INSR外显子进行扩增测序,同时在糖代谢正常及2型糖尿病人群中对发现的突变位点进行验证,通过MutationTaster、SIFT、PolyPhen2软件进行蛋白功能损害预测。先证者及其父亲的INSR第20号外显子均发现尚未报道的c.3652G/A杂合错义突变,导致Asp1218Asn突变,而糖代谢正常及2型糖尿病人群均不存在该位点突变。多种预测方法均提示该变异对基因/蛋白质结构或功能造成有害影响。INSR第20号外显子c.3652G/A杂合突变是新发现导致A型胰岛素抵抗综合征的致病性突变。This study aimed to identify mutations in the human insulin receptor gene(INSR)and investigate their role in the pathogenesis of severe insulin resistance syndrome.Sanger sequencing of the INSR gene was performed on a patient clinically suspected of having type A insulin resistance syndrome admitted to the Department of Endocrinology,the First Medical Center of Chinese PLA General Hospital.Upon identifying mutations,relevant exons were sequenced in her first-degree relatives.Additionally,control groups consisting of individuals with type 2 diabetes and those with normal glucose tolerance were screened for the mutation detected in the patient.Functional predictions of the INSR protein were made using MutationTaster,SIFT,and PolyPhen2 software.A previously unreported heterozygous missense mutation,c.3652G/A(Asp1218Asn),in exon 20 was identified in both the proband and her father.This mutation was not present in any of the control individuals.Multiple prediction tools indicate that this mutation likely disrupts gene/protein structure or function.The c.3652G/A(Asp1218Asn)heterozygous mutation in INSR is a novel variant that plays a significant role in the pathogenesis of severe insulin resistance in this Chinese family.

关 键 词：A型胰岛素抵抗综合征 胰岛素受体 基因突变 

分 类 号：R58[医药卫生—内分泌]