<i>MITF</i>基因在瓦登伯格综合征Ⅱ型中的突变分析

郭青; 刘梦潇; 李志祥; 张玉婷; 储九圣; 孔旭辉; 庞秀红

doi:10.7619/jcmp.20212187

MITF基因在瓦登伯格综合征Ⅱ型中的突变分析

郭青^{1, 2},
刘梦潇³,
李志祥³,
张玉婷³,
储九圣¹,
孔旭辉^1, ,,
庞秀红^1, ,

1.
扬州大学附属泰州市人民医院耳鼻咽喉-头颈外科, 江苏泰州, 225300
2.
扬州大学医学院, 江苏扬州, 225000
3.
大连医科大学, 辽宁大连, 116000

基金项目:

国家自然科学基金青年基金资助项目 81700920

江苏省基础研究计划(自然科学基金)面上项目 BK20191229

江苏省第五期“333工程”科研项目 BRA2019192

江苏省泰州市科技支撑(社会发展)项目 TS201733

江苏省卫生计生委科研课题项目 H201666

详细信息

通讯作者:
孔旭辉, E-mail: kongxuhui1966@163.com

庞秀红, E-mail: pxhzxy@163.com

中图分类号: R764.2;R764.3
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- 文章访问数: 401
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- PDF下载量: 19
出版历程
- 收稿日期: 2021-05-25
- 网络出版日期: 2021-08-31
- 发布日期: 2021-08-27

Analysis in mutation in MITF gene in type Ⅱ Waardenburg syndrome

1.
Department of Otolaryngology-Head and Neck Surgery, Taizhou People′s Hospital Affiliated to Yangzhou University, Taizhou, Jiangsu, 225300
2.
Medical College of Yangzhou University, Yangzhou, Jiangsu, 225000
3.
Dalian Medical University, Dalian, Liaoning, 116000

摘要

摘要:
目的探讨1例瓦登伯格综合征(WS)家系遗传性致病因素，以期通过遗传咨询而实现WS型耳聋的一级预防。
方法纳入三代5名家系成员(汉族)为研究对象，详细询问病史，采集外周静脉血并抽提DNA, 采用Sanger测序对3大常见耳聋基因和瓦登伯格综合征候选基因进行全序列筛查。
结果 MITF基因截短突变c.C763T(p.R255X)在该家系内呈现基因型-表型共分离。
结论截短突变c.C763T导致第255位精氨酸密码子突变为终止密码子，蛋白质合成提前终止，很可能为该家系的遗传性致病因素。MITF蛋白正常功能丧失所致的单倍体剂量不足很可能为该突变的致病机制。遗传咨询、婚育指导和产前诊断技术的应用，可避免由该突变导致的后代耳聋。
- MITF基因 /
- 截短突变 /
- 瓦登伯格综合征 /
- 单倍体剂量不足 /
- 遗传咨询
Abstract:
Objective To explore the genetic factors of a hereditary disease named Waardenburg syndrome (WS) in one case so as to achieve the goal of its prevention by genetic counseling.
Methods Five family members (Han nationality) of three generations were included in the study. Peripheral venous blood samples were collected and DNA was extracted after a detailed medical history inquiry. Mutation screening of all exons for three common deaf genes and six WS candidate genes was performed by Sanger sequencing.
Results The c.C763T (p.R255X) in MITF truncated mutation segregated with the phenotypes within the family.
Conclusion The truncated mutated p.R255X results in the mutation of the 255th arginine codon into termination codon, leading to premature termination of protein synthesis, which is probably the hereditary pathogenic factor of this family. The lack of haploid dose caused by the normal function loss of MITF protein is likely to be the pathogenic mechanism of this mutation. Genetic counseling, marital guidance and prenatal diagnostic techniques can prevent deafness in offspring caused by the mutation.
- MITF gene /
- truncated mutation /
- Waardenburg syndrome /
- haplo-insufficiency /
- genetic counseling

HTML全文

图 1 家系图、基因型-表型图和听力图

A: 家系图、基因型-表型图(正方形表示男性，圆形表示女性，黑色表示表型，白色表示正常); B: 家系内成员听力图。

下载: 全尺寸图片幻灯片

图 2 色素异常表型

A: Ⅰ-2面部斑点; B: Ⅱ-2面部斑点; C: Ⅲ-1面部斑点; D: Ⅱ-2右手斑点; E: Ⅰ-2双手斑点; F: Ⅰ-2双腿斑点; G: Ⅱ-2早白发; H: Ⅰ-2早白发; I: Ⅰ-2虹膜异色。

下载: 全尺寸图片幻灯片

图 3 突变峰图

Ⅲ-1、Ⅱ-2和Ⅰ-2为杂合突变，Ⅰ-1和Ⅱ-1为野生型。

下载: 全尺寸图片幻灯片

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