内科理论与实践

内科理论与实践 ›› 2025, Vol. 20 ›› Issue (03): 204-209.doi: 10.16138/j.1673-6087.2025.03.04

• 论著 • 上一篇    下一篇

1例线粒体DNA A3243G点突变病例家系临床表型和基因型分析

陈蕊华a, 丁晓颖a, 刘芳a, 王庆国b, 王育璠a()   

  1. 上海交通大学医学院附属第一人民医院 a.内分泌代谢科，上海 200080
    上海交通大学医学院附属第一人民医院 b.放射科，上海 200080
  • 收稿日期:2024-07-01 出版日期:2025-06-28 发布日期:2025-09-01
  • 通讯作者: 王育璠 E-mail:yyffwang@sina.com
  • 基金资助:
    国家科技重大专项项目(2023ZD0508104);上海市科学技术委员会科技计划项目(23ZR1451500)

Clinical features, diagnosis and phenotype and genotype analysis of a family with a mitochondrial DNA A3243G gene mutation

CHEN Ruihuaa, DING Xiaoyinga, LIU Fanga, WANG Qingguob, WANG Yufana()   

  1. a. Department of Endocrinology and Metabolism, Shanghai Jiao Tong University School of Medicine Affiliated First People’s Hospital, Shanghai 200080, China
    b. Department of Radiology, Shanghai Jiao Tong University School of Medicine Affiliated First People’s Hospital, Shanghai 200080, China
  • Received:2024-07-01 Online:2025-06-28 Published:2025-09-01
  • Contact: WANG Yufan E-mail:yyffwang@sina.com

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摘要：

目的：探讨母系遗传糖尿病伴耳聋综合征（maternally inherited diabetes and deafness syndrome, MIDD）合并脑动脉闭塞患者的临床、影像学特征及线粒体基因突变家系趋势。 方法：方法：通过对1例以糖尿病起病，后因耳聋、头晕和卒中样发作诊断为线粒体脑肌病伴高乳酸血症和卒中样发作（mitochondrial encephalomyopathy with lactic acidosis and stroke-like episode，MELAS）患者及其家系成员的诊疗，结合病史、实验室检查、影像学检查、基因检测及文献复习,分析该家系患者临床特点与致病基因异质性的关系。 结果：先证者存在典型的MIDD临床表现，其生化指标和影像学特征符合MIDD诊断。线粒体基因一代测序结果显示存在chrM:3243A > G(tRNA Leu1)突变,对先证者及其母系亲属进行血浆二代测序结果显示,先证者（Ⅲ-1）血液突变率为42.15%，母系亲属也大多存在不同程度点突变。 结论：MIDD患者临床表现复杂多样,易合并脑萎缩及脑血管闭塞，对于极度消瘦伴进行性听力减退的糖尿病患者应行基因检测和脑部影像学评估。二代测序有助于明确突变异质性，异质性越高，发病年龄越早，病情越重，需及早预防及诊治。

关键词: 线粒体糖尿病, 基因检测, 异质性

Abstract:

Objective To analyze the clinical and imaging characteristics of a patient with maternally inherited diabetes and deafness syndrome (MIDD) complicated with cerebral artery occlusion and explore the trend of mitochondrial gene mutations in her pedigree. Methods The study reviewed a patient with diabetes, deafness, dizziness and stroke like attack, who was diagnosed as mitochondrial encephalomyopathy with lactic acidosis and stroke-like episode (MELAS) syndrome and the medical history of her family members. Based on medical history, laboratory examinations, imaging examinations, genetic tests, and existing literature reports, the relationship between clinical characteristics of the patients in this family and pathogenic gene heterogeneity was analyzed. Results The proband presented typical clinical manifestations of MIDD, and the results of first-generation mitochondrial gene sequencing showed a chrM: 3243A>G (tRNA Leu1) mutation. Subsequently, next generation sequencing was performed using the blood of the proband and their maternal relatives, and the results showed that the blood mutation rate of proband was 42.15%, and most of the maternal relatives also exhibited different degrees of 3243A>G mutations. Conclusions The clinical manifestations of MIDD patients are complicated, and they are prone to brain atrophy and cerebrovascular occlusion. Sequencing analysis and early brain imaging evaluation is recommended to perform in diabetic patients with extreme emaciation and progressive hearing loss. Next-generation sequencing could help to clarify mutation heterogeneity. The higher heterogeneity and earlier onset age might indicate the more serious condition of the disease, which needs early prevention and diagnosis.

Key words: Mitochondrial diabetes mellitus, Gene detection, Heterogeneity

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