Waardenburg综合征2型家系的临床特征分析及突变检测

发布时间：2018-04-18 19:06

本文选题：Waardenburg综合征 + 小眼畸形相关转录因子　；参考：《临床耳鼻咽喉头颈外科杂志》2016年24期

【摘要】：目的:分析Waardenburg综合征(WS)2型家系的临床表型特征,并探讨其分子病因,为WS家系提供遗传咨询。方法:收集7个WS2型家系和散发病例(14例患者)的临床资料,分析其临床表型特征,均签署知情同意书并获取血样,提取基因组DNA,聚合酶链反应扩增MITF、SNAI2、SOX10和EDNRB基因编码区全部外显子,在ABI自动测序仪上进行正反向测序,并进行测序结果和相关数据信息的分析。结果:WS2型患者的临床表型特征最常见的是听力障碍(10/14,71.4%)、雀斑(7/14,50.0%)、虹膜异色(6/14,42.9%)和早白发(5/14,35.7%);耳聋表型比较一致,均表现为先天性双耳极重度感音神经性聋,雀斑表型不同于国外WS患者的皮肤低色素改变。突变检测发现WS02家系MITF基因第3号外显子c.328CT杂合突变(p.R110X),其他家系和散发病例均未检测到这4个基因的致病性突变。结论:WS2型患者表型特征多样,棕褐色雀斑沉着可能是国内WS患者皮肤色素异常表现的一种特殊形式。MITF基因突变R110X是导致WS02家系发病的分子病因,其他家系突变检测阴性提示存在其他未知的WS2致病基因或者拷贝数变异的可能。
[Abstract]:Objective: to analyze the clinical phenotypic characteristics of Waardenburg syndrome and explore its molecular etiology, and to provide genetic advice for WS families.Methods: the clinical data of 7 WS2 families and 14 sporadic patients were collected and their clinical phenotypic characteristics were analyzed. All of them signed informed consent letters and obtained blood samples.Genomic DNA was extracted and all exons of MITFSNAI2SOX10 and EDNRB gene coding region were amplified by polymerase chain reaction (PCR). Positive and negative sequencing was carried out on ABI automatic sequencing apparatus, and the sequencing results and related data information were analyzed.Results the most common phenotypic features of the patients with type W WS2 were 10 / 1471.4% hearing impairment, 7 / 1450.0% freckle, 6 / 1414 / 42.9% iridochroma and 5 / 141435.7m of early white hair, and the phenotypes of deafness were consistent, showing congenital diaural extremely severe sensorineural hearing loss.The phenotype of freckles is different from that of foreign WS patients.C.328CT heterozygosity at exon 3 of MITF gene was detected in WS02 family. No pathogenicity mutations of the four genes were detected in other families and sporadic cases.Conclusion the phenotypic features of patients with type W WS2 are diverse. Brown freckles may be a special form of skin pigmentation in WS patients in China. MITF gene mutation R110X may be the molecular cause of WS02.The negative detection of mutations in other families suggests that other unknown WS2 pathogenic genes or copy number mutations may exist.
【作者单位】：中南大学湘雅医院耳鼻咽喉头颈外科;中南大学湘雅医院神经外科;上海交通大学医学院附属仁济医院耳鼻咽喉头颈外科;
【基金】：国家自然科学青年科学基金项目(No:81500803,81301172) 国家自然科学基金面上项目(No:81470705,81260160) “973”国家重大科学研究计划项目(No:2014CB943003) 湖南省科技计划项目院士基金(No:2013FJ4110)联合资助
【分类号】：R764.43

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