Waardenburg综合征患儿眼部临床特点和基因突变分析  

Analysis of ocular clinical features and gene mutations of Waardenburg syndrome

作　　者：陈沁 佘凯芩 蒋善明 陆方[1] Chen Qin;She Kaiqin;Jiang Shanming;Lu Fang(Department of Ophthalmology,West China Hospital Sichuan University,Chengdu,610041)

机构地区：[1]四川大学华西医院眼科,成都610041

出　　处：《中华眼底病杂志》2021年第12期954-959,共6页Chinese Journal of Ocular Fundus Diseases

基　　金：四川省科技厅项目(2021YFS0210)。

摘　　要：目的观察Waardenburg综合征(WS)患儿眼部临床特征和基因突变位点。方法病例系列研究。2019年至2021年于四川大学华西医院眼科经临床及基因检查确诊的WS患儿3例纳入研究。其中,男性2例,女性1例;年龄分别为3、4、12个月。患儿均行外眼、眼前节、眼底和荧光素眼底血管造影检查,观察其眼部临床特征。抽取3例患儿外周静脉血,提取全基因组DNA行全外显子测序,分析其基因突变位点。结果3例患儿均有不同程度虹膜色素减少和眼底色素异常,并伴有感音神经性听力障碍;例1患儿同时存在内眦间距宽,例2患儿同时存在黄斑中心凹发育不良。基因测序结果显示,例1患儿配对盒基因3(PAX3)基因第2~8号外显子存在大片段杂合缺失,最终诊断为WSⅠ型;例2患儿小眼畸形相关转录因子(MITF)基因第9号外显子c.1066 C>T杂合突变、HPS6基因第1号外显子c.1417 G>T杂合突变,最终诊断为WSⅡ型;例3患儿SOX10基因第3号外显子c.497_500 delAAGA杂合缺失,最终诊断为WSⅣ型。PAX3和SOX10基因突变均为新发现突变。结论WS眼部临床特点包括虹膜色素减少和眼底色素异常、内眦异位;PAX 3基因第2~8号外显子大片段杂合缺失、MITF基因第9号外显子c.1066 C>T杂合突变、SOX10基因第3号外显子c.497_500 delAAGA杂合缺失分别是3例患儿的致病基因突变。Objective To deeply explore the clinical features and gene mutations of Waardenburg syndrome(WS)by tested of the eyes and genes of three patients.Methods A Case series study.From 2019 to 2021,3 children with WS who were diagnosed at Department of Ophthalmology,West China Hospital of Sichuan University were included in the study.Among them,there were 2 males and 1 female;the ages were 3,4,and 12 months,respectively.All children underwent external eye,anterior segment,fundus and fluorescein fundus angiography,the clinical features of the eyes were observed.The peripheral venous blood of 3 children was collected,and the whole genome DNA was extracted for whole exome sequencing to analyze the gene mutation sites.Results All children had different degrees of iris heterochromia and fundus pigment abnormalities,and were accompanied by sensorineural hearing impairment.Case 1 had dystopia canthorum;case 2 had macular fovea hypoplasia.The sequencing results of case 1 showed that there were large fragments of heterozygous deletion in exons 2-8 of the Paired box 3(PAX3)gene,who was diagnosed as WSⅠtype.The sequencing results of of case 2 showed heterozygous mutation in exon 9 of Microphthalmia-associated transcription factor(MITF)gene(c.1066 C>T),combined with heterozygous mutation in exon 1 of HPS6 gene(c.1417 G>T),who was diagnosed as WSⅡtype.The sequencing result of case 3 showed that the exon 3 of SOX10 gene had loss of heterozygosity(c.497_500 delAAGA),who was diagnosed as WSⅣtype.Both PAX3 and SOX10 gene mutations were newly discovered mutations.Conclusions The ocular clinical features of Waardenburg syndrome include hypopigmentation of the iris and choroid,and dystopia canthorum,etc.Early screening of the eye and hearing will help to better diagnose the disease.The large fragments of heterozygous deletion in exons 2-8 of the PAX3 gene,the heterozygous mutation in exon 9 of MITF gene(c.1066 C>T),and the loss of heterozygosity in exon 3 of SOX10 gene are pathogenic genetic variations of 3 children.

关 键 词：WAARDENBURG综合征 基因 突变 虹膜 眼底 

分 类 号：R725.9[医药卫生—儿科]