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目的通过对Waardenburg综合征II型(WSⅡ型)一家系临床分析和候选基因的突变检测,丰富了WSⅡ型的基因突变谱,并探讨WSⅡ型的分子遗传学特征。方法问卷式采集1个WSⅡ型家系的临床资料,绘制家系图谱,签署知情同意书并获取先证者及一级亲属的血样。通过聚合酶链反应(Polymerase chainreaction,PCR)扩增SOX10、SNAI2、PAX3、MITF、EDNRB和EDN3候选基因编码区的所有外显子。相应扩增产物酶切后进行测序,利用Mutation Surveyor 4.0软件及分子生物学网站的信息分析数据。结果根据患者及其母亲的临床表现和相关检查结果结合WSⅡ的诊断标准,为WSⅡ型;家系中SNAI2、PAX3、MITF、EDNRB和EDN3基因检测未发现突变;在家系先证者及母亲的SOX10基因的编码区发现了一个国内外尚未报道过的新突变SOX10(c.482del GTAGC),而在家系其他成员中均未发现此突变。结论此次研究对WSⅡ型一家系进行临床分析和基因突变研究,所发现的SOX10(c.482del GTAGC)基因突变国内外尚未见报道,属新突变;不仅丰富了人类基因突变数据库,而且为Waardenburg综合征的病因学研究和临床研究提供了有利资料。
OBJECTIVE: To enrich the genotypes of WS Ⅱ mutations and investigate the molecular characteristics of WS Ⅱ by clinical analysis and mutation detection of candidate genes in a Waardenburg syndrome type II (WS Ⅱ) pedigree. Methods The clinical data of one WS Ⅱ pedigree were collected by questionnaire, the pedigree was drawn, the informed consent was signed and the blood samples of probands and first-degree relatives were obtained. All exons of coding regions of SOX10, SNAI2, PAX3, MITF, EDNRB and EDN3 candidate genes were amplified by polymerase chain reaction (PCR). The corresponding amplified products were digested and sequenced, and the data were analyzed using Mutation Surveyor 4.0 software and molecular biology website information. Results According to the clinical manifestations of the patients and their mothers combined with the diagnostic criteria of WS Ⅱ, they were WS Ⅱ type. No mutation was found in the SNAI2, PAX3, MITF, EDNRB and EDN3 genes in the pedigrees. In the family probands and mothers, the SOX10 gene A new mutation SOX10 (c.482del GTAGC), which has not been reported in China and abroad, was found in the coding region, but not found in other members of the pedigree. Conclusions This study is to investigate the clinical analysis and gene mutation of WSⅡtype pedigree. The SOX10 (c.482del GTAGC) gene mutation found in this family has not been reported at home and abroad, which is a new mutation. It not only enriches the human gene mutation database, Syndrome etiology and clinical studies provide favorable information.