MITF基因在瓦登伯格综合征Ⅱ型中的突变分析

Analysis in mutation in MITF gene in type Ⅱ Waardenburg syndrome

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。

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.