【摘要】 目的通过对WS2的临床分析和候选基因的突变检测,加深对WS2的认识,并探讨Waardenburg综合征2型的分子遗传学特征。方法收集一就诊于湘雅医院耳鼻咽喉科门诊的湖南家系,做出临床诊断,签署知情同意书获取血样。聚合酶链反应(polymerase chain reaction,PCR)扩增MITF、SNAI2、SOX10基因编码区的全部外显子,扩增的PCR产物酶切后在ABI3100自动测序仪上进行正反向直接测序分析,利用GeneTool软件及遗传学网站的信息分析数据。结果 (1)2位患者诊断为WS2;(2)先证者及先证者母亲的SOX10基因的编码区找到了一个国内外未曾报道过的杂合子新突变(c.113delG,p.Gly38AlafsX71),在家系中其他成员和100名家系外健康对照者中均未发现此突变。MITF和SNAI2基因突变检测均正常。结论 (1)本研究对Waardenburg综合征Ⅱ型一家系进行了临床特征和基因突变分析,有助于对该综合征的进一步认识;(2)所发现的SOX10基因(c.113delG,p.Gly38AlafsX71)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,而且为更好地了解该基因的功能提供了新的线索;(3)WS2患者在做基因筛查时SOX10和MITF要作为候选基因。更多还原

【Abstract】 Objiective To increase understanding of Waardenburg syndrome type 2(WS2) and study its molecular genetic mechanisms through WS2 case analysis and screening of candidate genes for mutations.Methods Pedigrees seen at the Otolaryngology Clinic,Xiangya Hospital,were identified.The proband was primarily diagnosed with WS2.Detailed histories were collected together with thorough physical examinations.The diagnosis was confirmed and pedigrees plotted Informed consents were obtained from participants before collecting blood samples.Genomic DNA was extracted from each individual and complete MITF,SNAI2,SOX10 gene coding exons were amplified using specific PCR primers.Direct sequencing was carried out to identify mutations.The raw data were analyzed with the Gene Tool software and molecular biological website references.Results(1) Two patients were diagnosed as Waardenburg syndrome type II based on relevant diagnostic criteria.(2) A heterozygous SOX10 frame shift mutation(c.113delG) on exon 3 was identified in the probands and their mothers,but not in other family members or healthy controls.In this frame shifting change,Glycine-38 was the first affected amino acid and replaced by a Alanine,creating a new reading frame ending in a stop at position 71(p.Gly38AlafsX71).There were no MITF or SNAI2 gene mutations.Conclusions(1) A novel deletion mutation in the sox10 gene has been identified in two families with typical Waardenburg syndrome type 2 patients.(2) The molecular findings increase our understanding of the function of sox10 gene and enrich the human gene mutation database.(3) More importantly,SOX10 deletions should be considered as first-step analysis in WS2,as well as MITF mutations.更多还原