全外测序联合拷贝数变异检测在遗传性耳聋的应用
Whole Exon Sequencing Combined with Copy Number Variation Detection for Hereditary Deafness
张远辉 1林颖 2陈艺文 1刘小萍 1于锋2
作者信息
- 1. 广州市红十字会医院(广州市应急医院,暨南大学附属广州市红十字会医院,广州市红十字会医院互联网医院,广州 510220)
- 2. 广州市红十字会医院(广州市应急医院,暨南大学附属广州市红十字会医院,广州市红十字会医院互联网医院,广州 510220);暨南大学耳鼻喉头颈外科研究所
- 折叠
摘要
目的 探讨全外显子测序(WES)联合拷贝数变异(CNV)检测在遗传性耳聋中的临床应用价值,并加深对CNV的认识.方法 选取广州市红十字会医院耳鼻咽喉头颈外科就诊的双耳中度感音神经性聋患儿,无家族遗传史、用药史,完善内镜、影像学、主观和客观听力学等检查,采集外周血样本,行WES寻找致聋原因并验证.结果 患儿无家族遗传史、耳毒性药物用药史等,听性脑干反应阈值、ASSR及纯音听阈测听提示双侧中度感音神经性聋.在该患儿全外显子组发现12个纯合变异,分别定位于1(CR1基因,剪接变异)、5(ZSWIM6基因、SMN1基因,同义突变)、6(ATXN1基因,框内缺失突变;TENT5A基因,框内插入突变)、7(CFTR基因,内含子)、8(TG,启动子)、9(PRDM12基因,框内缺失突变)、10(TUBGCP2基因,剪接变异)、11(TENM4基因,剪接变异)、15(STRC基因,缺失)、16(ABCC11基因,错义变异)号染色体.根据美国医学遗传学与基因组学学会指南、综合病史分析,只有STRC基因NM_153700.2:EX1-EX29E Del变异为致病变异,其余变异为良性或可能良性.多重链接探针扩增技术对靶序列进行验证,结果证实.结论 本例患儿为DFNB16(OMIM:603720)的STRC基因变异导致双耳中度感音神经性聋.临床诊疗中,可根据病史,选择不同深度、广度的检测技术;加强耳科医师对CNV引起遗传性耳聋的认识.
Abstract
Objective To determine the value of whole exon sequencing(WES)combined with copy number vari-ation(CNV)detection in diagnosis of hereditary deafness,and to further understanding of CNV.Methods A child with binaural moderate sensorineural hearing loss without a family history of genetic disorders or a history of ototoxic medi-cation was admitted to our department.Endoscopy,imaging,subjective and objective audiologic examinations were completed.Peripheral blood samples were collected,and WES was performed to identify the cause of the child's deaf-ness,with the target sequence confirmed by multiple ligation-dependent probe amplification(MLPA).Results Audio-metric,ABR and ASSR thresholds indicated moderate sensorineural deafness.WES showed 12 homozygous variants lo-cated in chromosomes 1(CR1 gene,splice-20),5(ZSWIM6 gene and SMN1 gene,coding-synon),and 6(ATXN1 gene,cds-del;TENT5A,cds-ins),7(CFTR gene,intron),8(TG,promoter),9(PRDM12 gene,cds-del),10(TUBGCP2 gene,splice+20),11(TENM4 gene,splice+20),15(STRC gene,deletion)and 16(ABCC11 gene,missense).Based on ACMG guidelines and comprehensive history analysis,only the STRC gene variant(NM_153700.2:EX1-EX29E Del)was deter-mined to be pathogenic,while the rest variants were considered benign or potentially benign.The target sequence was verified by MLPA.Conclusion Deletion of DFNB16(OMIM:603720)in the STRC gene caused bilateral moderate sen-sorineural deafness in this case.In the clinic,a wide range of detection techniques at various levels can be selected for diagnosis purposes based on the patient's medical history.Such knowledge can enhance the understanding of CNV and its relations to hereditary deafness among otologists.
关键词
全外显子测序/拷贝数变异/感音神经性耳聋/多重链接探针扩增技术Key words
whole exon sequencing/copy number variation/sensorineural deafness/multiple ligation-dependent probe amplification引用本文复制引用
基金项目
广州市科技计划(2023A03J0520)
广州市科技计划(2023A03J0521)
广州市临床高新技术项目(2023C-GX05)
广州市临床高新技术项目(2019GX08)
出版年
2024
国家科技期刊平台
NSTL
万方数据