一个PCDH15基因变异所致的Usher综合征家系的遗传学分析及产前诊断  

Genetic analysis and prenatal diagnosis of a Chinese pedigree affected with Usher syndrome due to novel compound heterozygous variants of PCDH15 gene

作　　者：杨科 张玉薇 娄桂予 祁娜 张冰 康冰 雷星星 廖世秀 Yang Ke;Zhang Yuwei;Lou Guiyu;Qi Na;Zhang Bing;Kang Bing;Lei Xingxing;Liao Shixiu(Medical Genetic Institute of Henan Provincial People’s Hospital,People’s Hospital of Zhengzhou University,Henan Provincial People’s Hospital,Zhengzhou,Henan 450003,China)

机构地区：[1]河南省人民医院,郑州大学人民医院,河南省医学遗传研究所,郑州450003

出　　处：《中华医学遗传学杂志》2022年第3期305-308,共4页Chinese Journal of Medical Genetics

基　　金：河南省医学科技攻关计划(LHGJ20190594,LHGJ20200006)。

摘　　要：目的对1个Usher综合征家系的临床特征及基因变异进行分析,明确其遗传病因。方法对家系中患儿进行全外显子测序,就发现的可疑致病变异用Sanger测序法对患儿及其父母进行检测,明确先证者病因后,进一步对家系中的胎儿进行产前诊断。结果测序结果显示先证者PCDH15基因(NM;33056)存在c.17;8insA(p.Tyr6Ter*)及c.4095;096insA(p.Arg1366Lys fs*38)复合杂合变异,变异分别来源于其父母。同时对100名正常人DNA进行PCDH15基因(NM;33056)c.17;8insA及c.4095;096insA变异筛查均未发现相同变异。根据美国医学遗传学与基因组学学会遗传变异分类标准与指南,以上两个变异判定为致病性变异(PVS1+PM2+PP4)。经验证,胎儿为PCDH15基因(NM;33056)c.4095;096insA变异携带者,预测胎儿不会出现Usher综合征,该胎儿出生后通过了新生儿听力筛查,至1岁多未发现明显听觉、视觉功能异常。结论PCDH15基因(NM;33056)c.17;8insA(p.Tyr6Ter*)及c.4095;096insA(p.Arg1366Lys fs*38)插入移码变异可能是该家系罹患Usher综合征的遗传病因。Objective To analyze the clinical features and genetic variant in a patient with Usher syndrome.Methods Whole exome sequencing was carried out for the patient.Suspected variants were validated by Sanger sequencing of her parents and fetus.Results The proband was found to harbor compound heterozygous variants c.17_18insA(p.Tyr6Ter*)and c.4095_4096insA(p.Arg1366Lys fs*38)of the PCDH15 gene(NM_033056),which were respectively inherited from her father and mother.The same variants were not detected in 100 healthy controls.Based on the guidelines of the American Society of Medical Genetics and Genomics,both variants were predicted to be pathogenic(PVS1+PM2+PP4).By prenatal diagnosis,her fetus was found to carry the c.4095_4096insA variant.After birth,the child has passed neonatal hearing screening test,and no abnormal auditory and visual function was found after the first year.Conclusion The compound heterozygous variants c.17_18insA(p.Tyr6Ter*)and c.4095_4096insA(p.Arg1366Lys fs*38)of the PCDH15 gene probably underlay the Usher syndrome is this proband.

关 键 词：USHER综合征 PCDH15基因 基因变异 

分 类 号：R725.9[医药卫生—儿科]