一例新的胰岛素受体突变相关的严重胰岛素抵抗综合征  

One case of severe insulin resistance syndrome associated with a novel insulin receptor mutation

作　　者：胡卓萌 倪启程 陈于菲 韩如来 程倩云 石娟[1] 叶蕾[1] 王卫庆[1] 张翼飞[1] Hu Zhuomeng;Ni Qicheng;Chen Yufei;Han Rulai;Cheng Qianyun;Shi Juan;Ye Lei;Wang Weiqing;Zhang Yifei(Department of Endocrine and Metabolic Diseases,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai Institute of Endocrine and Metabolic Diseases,Shanghai National Clinical Research Center for Metabolic Diseases,Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission,Shanghai Key Laboratory for Endocrine Tumor,Shanghai 200025,China)

机构地区：[1]上海交通大学医学院附属瑞金医院内分泌代谢病科,上海市内分泌代谢病研究所,国家代谢性疾病临床医学研究中心(上海),国家卫生健康委员会内分泌代谢病重点实验室,上海市内分泌肿瘤重点实验室,上海200025

出　　处：《中华内分泌代谢杂志》2024年第12期1059-1064,共6页Chinese Journal of Endocrinology and Metabolism

基　　金：2022年东方英才计划领军项目(153);四大慢病重大专项(2023ZD0508100)。

摘　　要：胰岛素受体(insulin receptor,INSR)基因突变相关的严重胰岛素抵抗综合征在临床中并不常见。本研究对1例严重胰岛素抵抗的患儿进行胚系DNA全外显子组测序,并经PCR-Sanger测序验证,明确存在新的INSR基因突变。该13岁女性患儿存在胰岛素抵抗,伴有黑棘皮表现、安氏Ⅱ类错颌畸形。其母亲、外祖母均有高胰岛素血症。同时,基因诊断确认家系中先证者及其母亲、外祖母都携带INSR基因杂合变异c.637delA(p.S213Vfs*69)。这种新的INSR c.637delA突变导致蛋白质第213位的丝氨酸被缬氨酸取代,并且经多种计算机软件程序预测其为致病性变异。本例患儿是INSR基因突变相关的严重胰岛素抵抗病例,其临床表型介于Rabson-Mendenhall综合征和A型胰岛素抵抗综合征之间,较难区分。长期随访以评估其疾病进展和远期预后尤为重要。Severe insulin resistance syndrome associated with mutations in the insulin receptor(INSR)gene is rare in clinical practice.We report a 13-year-old female patient with insulin resistance,acanthosis nigricans,and ClassⅡmalocclusion,whose family history included hyperinsulinemia in both her mother and grandmother.Whole-exome sequencing and PCR-Sanger validation identified a novel INSR mutation,c.637delA(p.S213Vfs*69),resulting in a pathogenic variant that substitutes serine at position 213 with valine.This case highlights a clinical phenotype that is challenging to differentiate between Rabson-Mendenhall syndrome and A-type insulin resistance syndrome.Long-term follow-up is crucial to assess disease progression and prognosis.

关 键 词：胰岛素抵抗 高胰岛素血症 胰岛素受体 基因诊断 

分 类 号：R58[医药卫生—内分泌]