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中华诊断学电子杂志 ›› 2017, Vol. 05 ›› Issue (01) : 46 -50. doi: 10.3877/cma.j.issn.2095-655X.2017.01.013

所属专题: 文献

临床研究

线粒体基因突变糖尿病一家系分析
齐婷1, 王述进1, 张彦1, 张李钰2, 左红1, 黎国红1, 牛瑜1, 冯佳1, 马磊1, 刘旭峰1, 杨华1, 刘宋芳1, 杨颖2,()   
  1. 1. 710054 西安市第九医院内分泌科
    2. 710002 西安市儿童医院陕西省儿科疾病研究所
  • 收稿日期:2016-07-06 出版日期:2017-02-26
  • 通信作者: 杨颖
  • 基金资助:
    西安市科技计划项目[SF1510(4)

Genetic and clinical characteristics of a family with diabetes caused by mitochondrial gene mutation

Ting Qi1, Shujin Wang1, Yan Zhang1, Liyu Zhang2, Hong Zuo1, Guohong Li1, Yu Niu1, Jia Feng1, Lei Ma1, Xufeng Liu1, Hua Yang1, Songfang Liu1, Ying Yang2,()   

  1. 1. Department of Endocrinology, The Ninth Hospital of Xi'an, Xi'an 710054, China
    2. Department of Pediatric Disease Research Institute, Xi′An Children′s Hospital, Xi′An 710002, China
  • Received:2016-07-06 Published:2017-02-26
  • Corresponding author: Ying Yang
  • About author:
    Corresponding author: Yang Ying, Email:
引用本文:

齐婷, 王述进, 张彦, 张李钰, 左红, 黎国红, 牛瑜, 冯佳, 马磊, 刘旭峰, 杨华, 刘宋芳, 杨颖. 线粒体基因突变糖尿病一家系分析[J/OL]. 中华诊断学电子杂志, 2017, 05(01): 46-50.

Ting Qi, Shujin Wang, Yan Zhang, Liyu Zhang, Hong Zuo, Guohong Li, Yu Niu, Jia Feng, Lei Ma, Xufeng Liu, Hua Yang, Songfang Liu, Ying Yang. Genetic and clinical characteristics of a family with diabetes caused by mitochondrial gene mutation[J/OL]. Chinese Journal of Diagnostics(Electronic Edition), 2017, 05(01): 46-50.

目的

对一线粒体基因突变糖尿病家系临床特点及基因突变结果进行分析,以提高临床对线粒体基因突变糖尿病的认识。

方法

提取家系成员外周血脱氧核糖核酸(DNA),采用靶向捕获的二代测序技术对先证者的线粒体基因组及其相关的核基因进行分析,家系内其他成员采用一代测序进行验证,同时收集家系的临床资料。

结果

参加调查的8位家系成员中,检测到线粒体DNA(mtDNA)3243A>G突变的有3例,其中已经发病的糖尿病患者2例,另有1例糖尿病患者并未检测到mtDNA 3243A>G突变。2例糖尿病患者发病年龄在40岁以前,3例糖尿病患者体重指数(BMI)偏低,自身免疫性糖尿病抗体阴性,伴随有神经性耳聋。1例成员虽有3243基因位点突变,但尚未表现为糖尿病。

结论

mtDNA 3243A>G突变为该家系糖尿病发病的原因,其临床表现符合发病早、体质量低、伴随神经性耳聋的特点。

Objective

To analyze the clinical characteristics and gene mutation results in a family with diabetes, in order to improve the knowledge of the diabetes caused by mitochondrial gene mutation.

Methods

Genomic DNA was extracted using standard procedure from peripheral blood of the family members, and targeted next generation sequencing was performed on the proband to capture and sequence the entire mtDNA and nuclear genes related to mitochondrial structure and function.Moreover, other patients and members from the family were performed directed sanger sequence to detect the genetic information of the mitochondrial genes.Meanwhile clinical data were collected and analyzed.

Results

mtDNA 3243A>G mutation was detected in 3 of 8 members in the family.Among these 3 members, 2 cases were diagnosed diabetes by the onset before the age of 40, with low body mass index (BMI), negative autoimmune diabetes antibody and accompanied by nerve deafness.In addition, another member aged 10 was detected mtDNA 3243A>G mutation without clinical diabetes characteristics until now.

Conclusion

mtDNA 3243A>G mutation is the cause of the diabetes of this family, and the clinical manifestation of the patients with early onset, low body weight and nerve deafness conforms to the mitochondrial diabetes.

图1 3243线粒体基因突变糖尿病一例家系谱图。Ⅰ~Ⅲ 代表世代数;1~9代表子女数;为家系中糖尿病患者;□○为家系中血糖正常者;为家系中先证者。
图2 先证者线粒体基因组的二代测序数据分析。显示mtDNA 3243A>G突变频率为21.00%(红色箭头所指为mtDNA 3243A>G突变位点)
图3 糖尿病家系内mtDNA 3243A>G突变的一代测序峰图。箭头所指为突变位点
表1 先证者线粒体基因组所检测到的多态性位点信息
表2 线粒体基因突变糖尿病家系成员3243点突变情况及临床资料
表3 线粒体基因突变糖尿病家系中3例mtDNA 3243位点突变者及Ⅰ2临床特点
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