阶梯式耳聋基因诊断策略及其临床实践  

A step-by-step approach for hearing loss diagnosis and its clinical practice

作　　者：刘畅[1] 黄演林[1] 汪安石[1] 张彦[1] 丁红珂[1] 曾玉坤[1] 刘渊[1] 刘玲[1] 吴菁[1] 尹爱华[1] LIU Chang;HUANG Yanlin;WANG Anshi;ZHANG Yan;DING Hongke;ZENG Yukun;LIU Yuan;LIU Ling;WU Jing;YIN Aihua(Medical Genetic Center,Guangdong Women and Children Hospital,Guangzhou,Guangdong,China,510010)

机构地区：[1]广东省妇幼保健院医学遗传中心,广东广州511400

出　　处：《分子诊断与治疗杂志》2022年第1期6-9,共4页Journal of Molecular Diagnostics and Therapy

基　　金：广东省医学科学技术研究基金项目(A2020302)。

摘　　要：目的建立阶梯式耳聋基因诊断策略,应用于临床诊疗实践,以提高诊断效率、降低检测成本改善病人管理。方法选取2017年1月至2020年12月广东省妇幼保健院医学遗传中心226例耳聋患者进行基因诊断。阶梯式诊断策略第一阶梯采用微阵列芯片法对受检者进行GJB2、GJB3、SLC26A4及线粒体DNA 12S NrRA基因上中国人群耳聋基因变异热点检测。第二阶梯基因诊断采用Sanger测序法对受检者进行GJB2、SLC26A4等中国人群中较常见的耳聋基因测序。第三阶梯基因诊断采用全外显子测序法,主要用于第一、二阶梯未检出或检出结果不能解释表型的耳聋病患,但对于有急切产前诊断需求等检测时间窗较短的耳聋患者可直接接受高通量测序检测。结果第一阶梯基因检测为14例病患明确分子诊断(诊断率8.5%),第二阶梯基因检测为24例病患明确分子诊断(诊断率15.9%),第三阶梯基因检测额外提高了32.4%的诊断率。而在选择直接接受全外显子组测序检测的人群中诊断率为44.3%。结论本研究建立了一种阶梯式耳聋基因诊断策略,并将其应用于临床诊疗,实践效果显示分层递进式检测更为经济。但对于部分检测时间窗较短的耳聋患者,直接行高通量测序检测,效率更高。明确耳聋患者分子诊断有助于提高病人管理、改善患者预后、规范遗传咨询及再发风险评估。Objective To establish a stepwise approach for hearing loss diagnosis and apply it to clinical practice to improve the diagnosis efficiency,reduce the testing costs,and improve the patient management.Methods A total of 226 hearing loss patients were enrolled from January 2017 to December2020 for genetic diagnosis.The first step of the stepwise approach used the allele-specific PCR-based universal array to detect hot-spot mutations in GJB2,GJB3,SLC26 A4 and mitochondrial DNA 12 S rRNA genes.Sanger sequencing was used as the second step to examine the comparatively common hearing loss-associated genes in Chinese population,such as GJB2 and SLC26 A4 genes.The whole exome sequencing was used as the third step to detect hearing loss patients who were not molecularly diagnosed in the first and second steps.But for patients with a short detection time window,the next generation sequencing can be employed directly.Results The first step genetic testing confirmed molecular diagnosis for 14 patients(diagnosis rate 8.5%),the second step genetic testing confirmed molecular diagnosis for 24 patients(diagnosis rate 15.9%),and the third step genetic testing increased an additional 32.4%of diagnosis rate.The diagnostic rate was 44.3%in the population who chose to undergo direct whole-exome sequencing testing.Conclusion This study established a step-bystep deafness genetic diagnosis strategy and applied it to clinical diagnosis and treatment.The practice effect showed that the stratified progressive detection was more economical.However,for some deaf patients with a short detection time window,it is more efficient to directly perform high-throughput sequencing detection.A clear molecular diagnosis of deafness patients can help improve patient management,improve patient prognosis,standardize genetic counseling,and assess recurrence risk.

关 键 词：遗传性耳聋 基因诊断 Sanger测序法 微阵列芯片法 全外显子组测序法 

分 类 号：R764.43[医药卫生—耳鼻咽喉科]