Usher综合征Ⅱ型患儿临床表型及USH2A基因突变分析  

Phenotype and USH2A gene mutation in children with Usher syndrome type II

作　　者：潘澍青 潘小莉 鲍幼维 李海波 庄丹燕 PAN Shuqing;PAN Xiaoli;BAO Youwei;LI Haibo;ZHUANG Danyan(Center for Comprehensive Prevention and Treatment of Birth Defects,Women and Children's Hospital Affiliated to Ningbo University,Ningbo Key Laboratory for Prevention and Treatment of Embryogenic Diseases,Ningbo Key Laboratory of Genomic Medicine and Birth Defects Prevention,Ningbo 315012,China)

机构地区：[1]宁波大学附属妇女儿童医院出生缺陷综合防治中心、宁波市胚胎源性疾病防治重点实验室、宁波市基因组医学与出生缺陷防治重点实验室,315012

出　　处：《浙江医学》2024年第15期1580-1584,1590,共6页Zhejiang Medical Journal

基　　金：浙江省医药卫生科技计划项目(2023KY1121);宁波市科技计划项目(2022S035);宁波市医疗卫生高端团队重大攻坚项目(2022020405);宁波市医学重点学科建设项目(2022-F26)。

摘　　要：目的探讨Usher综合征Ⅱ型患儿USH2A基因的变异类型和临床表型,明确其致病原因,为临床诊断提供参考依据。方法回顾性分析2022年6月至2023年6月在宁波大学附属妇女儿童医院确诊的3例Usher综合征Ⅱ型患儿的临床资料,采集患儿及其父母的外周血样,应用全外显子组测序技术对患儿进行检测,并用Sanger测序技术对疑似致病变异及患儿父母进行位点验证。结果3例患儿均存在双耳轻度到中度听力损失,视力正常,未出现前庭反应。例1检出USH2A基因:c.8559-2A>G/c.1964G>C(p.C655S)复合杂合变异。例2检出USH2A基因:c.1644+4A>G/c.187C>T(p.R63*)复合杂合变异。例3检出USH2A基因:c.13877_13880del(p.Q4626Pfs*7)/c.7232A>C(p.Q2411P)复合杂合变异。例1和例2遗传自亲代,例3未接受亲代验证。根据美国医学遗传学与基因组学学会相关指南,USH2A基因c.8559-2A>G、c.187C>T(p.R63*)和c.13877_13880del(p.Q4626Pfs*7)变异评为致病性变异;USH2A基因c.1644+4A>G评为可能致病性变异;USH2A基因c.1964G>C(p.C655S)和c.7232A>C(p.Q2411P)评为临床意义未明变异。c.1964G>C(p.C655S)变异查询文献和数据库均未见报道和收录。结论USH2A基因复合杂合变异可能是3例患儿的致病原因;本研究结果不仅丰富了USH2A基因的变异谱,也为临床诊断提供参考依据。Objective To investigate the phenotypes and USH2A gene mutation in children with Usher syndrome type II.Methods Clinical data of 3 pediatric patients with Usher syndrome type II diagnosed in Women and Children's Hospital Affiliated to Ningbo University from June 2022 to June 2023 were retrospectively analyzed.Whole exome sequencing was used for genetic diagnosis of patients,and Sanger sequencing technique was used to verify the suspected pathogenic mutations in patients and their family members.Results All three patients had mild to moderate hearing loss in both ears,normal vision,and no vestibular reactions.USH2A gene mutation was detected in patient 1:c.8559-2A>G/c.1964G>C(p.C655S)complex heterozygous mutation;in patient 2:c.1644+4A>G/c.187C>T(p.R63*)complex heterozygous mutation,and in patient 3:c.13877_13880del(p.Q4626Pfs*7)/c.7232A>C(p.Q2411P)complex heterozygous mutation.Patient 1 and patient 2 were inherited from their parents,while in patient 3 family members did not receive gene tests.According to the American College of Medical Genetics and Genomics guidelines,USH2A gene c.8559-2A>G,c.187C>T(p.R63*)andc.13877_13880del(p.Q4626Pfs*7)were rated as pathogenic mutations;USH2A gene c.1644+4A>G was rated as a possible pathogenic variation;USH2A gene c.1964G>C(p.C655S)and c.7232A>C(p.Q2411P)were rated as unknown mutations of clinical significance;while c.1964G>C(p.C655S)variation was not reported or included in the literature and database.Conclusion USH2A gene complex heterozygous variation may be the cause of deafness in 3 patients.These studies not only enrich the variation spectrum of USH2A gene,but also provide reference for clinical diagnosis.

关 键 词：Usher综合征Ⅱ型 全外显子组测序 USH2A基因 Sanger测序 

分 类 号：R725.9[医药卫生—儿科]