全外显子组测序技术在成人遗传病中的应用

Analysis of Whole Exome Sequencing Result in Adult Genetic Diseases

目的探讨全外显子组测序(WES)在成人遗传病分子诊断中的应用。方法回顾性病例分析。以2021年8月至2022年12月于复旦大学附属中山医院就诊的445例成人遗传病疑诊患者(18~80岁)为研究对象。通过WES对患者进行基因检测分析,采用美国医学遗传学与基因组学学会制定的序列变异解读指南进行检出变异的致病性分析。根据WES检测数据、临床表型和基因型进一步分析患者临床特征。结果成人疑诊遗传病患者的WES阳性检出率为28.08%(125/445),其中41~50岁患者阳性检出率最高,为34.33%(23/67)。125例成人遗传病患者共检出133种遗传病,心血管(63.16%,84/133)、神经(18.05%,24/133)和内分泌系统(13.53%,18/133)受累比例排前3位;成人遗传病中主要包括肥厚型心肌病(18.80%,25/133)、扩张型心肌病(16.54%,22/133)、马凡综合征(15.04%,20/133)、癫痫(9.02%,12/133)和家族性高胆固醇血症(4.51%,6/133),主要致病基因包括FBN1(14.29%,19/133)、MYBPC3(9.02%,12/133)、MYH7(9.02%,12/133)、LDLR(3.76%,5/133)、TTN(3.76%,5/133)和TNNI3(3.01%,4/133)基因。结论WES是成人遗传病诊断的有效检测方法,尤其在心血管、神经和内分泌系统受累的成人遗传病患者中阳性检出率较高。

ObjectiveTo investigate the effectiveness and feasibility of whole exome sequencing(WES),as a molecular diagnosis technique,for adult patients with genetic diseases.MethodsThe present retrospective analysis included 445 adult patients(ages 18-80 years)with suspected genetic diseases who underwent whole exome sequencing(WES)from August 2021 to December 2022.The pathogenicity classification of each variant was assessed in accordance with the recommendations developed by the American Society of Medical Genetics and Genomics.ResultsThe overall positive rate of WES among adult patients with suspected genetic diseases was 28.08%(125/445).The highest positive rate was observed in the age group of 41-50 years(34.33%,23/67).Among the diagnosed genetic diseases,those affecting the cardiovascular system(63.16%,84/133),nervous system(18.05%,24/133),and endocrine system(13.53%,18/133)ranked as the top three.The most common genetic diseases identified through WES in adult patients were hypertrophic cardiomyopathy(18.80%,25/133),dilated cardiomyopathy(16.54%,22/133),Marfan syndrome(15.04%,20/133),epilepsy(9.02%,12/133),and familial hypercholesterolemia(4.51%,6/133).The main causative genes identified included FBN1(14.29%,19/133),MYBPC3(9.02%,12/133),MYH7(9.02%,12/133),LDLR(3.76%,5/133),TTN(3.76%,5/133),and TNNI3(3.01%,4/133).ConclusionApplying the WES technique in clinical practice can improve the diagnostic rate of adult genetic diseases,especially in adult patients with suspected genetic conditions involving the cardiovascular system,nervous system,and endocrine system.