NOG基因移码变异导致的听力异常家系的遗传学分析及产前诊断  

Genetic analysis and prenatal diagnosis of a novel frame-shift variant of noggin gene in a family with hearing loss

作　　者：嵇龙飞 蔡云祥[1] 沈学萍 姚娟 范丽红 JI Long-fei;CAI Yun-xiang;SHEN Xue-ping;YAO Juan;FAN Li-hong(Clinical Laboratory,the First People’s Hospital of Huzhou,Zhejiang 313000,China;不详)

机构地区：[1]湖州市第一人民医院检验科,浙江313000 [2]湖州市妇幼保健院产前诊断中心

出　　处：《中国卫生检验杂志》2023年第16期1960-1962,1967,共4页Chinese Journal of Health Laboratory Technology

基　　金：湖州市科学技术局公益性应用研究项目(2020GY26);浙江省医药卫生科技计划项目面上项目计划(2021K Y1085)。

摘　　要：目的探讨一个听力损失家系的遗传学病因,并根据基因检测结果进行产前诊断。方法对先证者进行了靶向下一代测序(next-generation sequencing,NGS),其中包含5679个与听力损失相关的基因。NGS检测到的变异通过Sanger测序进行验证,并评估其致病性,通过羊膜穿刺术进行产前诊断。结果测序分析在noggin(NOG)基因中发现了一个移码变异c.509delC(p.Pro170ArgfsTer4),该变异导致一个截断的蛋白质。目前,该突变未被任何数据库或出版物收录及报道,进一步生物信息学分析预测该变异为致病变异。产前诊断提示该胎儿没有携带同样的突变。结论对该家系的分析显示NOG基因的c.509delC(p.Pro170ArgfsTer4)突变导致先证者混合性听力损失和轻度骨骼异常,这与以往的研究不同。本研究对进一步研究NOG基因突变的临床表型和发病机制具有重要意义。Objective This study aims to explore the genetic etiology in a family hearing loss.Prenatal diagnosis was also conducted based on the genetic test results.Methods A targeted next-generation sequencing(NGS)gene panel comprised of 5679 genes associated with hearing loss on the proband was performed.Variants detected by NGS were validated by Sanger sequencing and evaluated for pathogenicity.Amniocentesis was performed for prenatal diagnosis.Results The sequencing analysis identified a frameshift variant in the noggin(NOG)gene,c.509delC(p.Pro170ArgfsTer4),which leads to a truncated protein.The mutation was not recorded in any database or any previous publication.Bioinformatics analysis further predicted this variant as a disease-causing variant.Prenatal diagnosis suggested that the fetus didn’t take the same mutation.Conclusion Analysis of this family showed that the c.509delC(p.Pro170ArgfsTer4)mutation in the NOG gene resulted in mixed hearing loss and mild skeletal abnormality,which is different from the previous studies.The study is of great importance for further studies on the clinical phenotype and pathogenesis of the NOG mutation.

关 键 词：听力损失 下一代测序 noggin基因 混合型 产前诊断 

分 类 号：R714.5[医药卫生—妇产科学]