神经发育障碍儿童的全外显子组测序分析与产前诊断  

Whole exome sequencing analysis and prenatal diagnosis in children with neurodevelopmental disorders

作　　者：秦亚运 姚妍怡[1] 刘念[1] 王波[1] 刘丽君 李卉 高唐鑫子 徐闰红 王小艳 宋婕萍[1] Qin Yayun;Yao Yanyi;Liu Nian;Wang Bo;Liu Lijun;Li Hui;Gao Tangxinzi;Xu Runhong;Wang Xiaoyan;Song Jieping(Medical Genetics Center,Maternal and Child Health Hospital of Hubei Province,Wuhan 430070,China)

机构地区：[1]湖北省妇幼保健院医学遗传中心,武汉430070

出　　处：《中华预防医学杂志》2023年第5期753-759,共7页Chinese Journal of Preventive Medicine

摘　　要：探讨全外显子组测序(WES)在产前和产后神经发育障碍(NDDs)诊断中的应用价值。本研究回顾性分析2020年6月至2022年3月在湖北省妇幼保健院优生遗传门诊就诊的70例NDDs儿童的临床资料,另有28例为NDDs相关的产前诊断病例,利用WES以明确遗传病因。将基于WES的拷贝数变异(CNV)分析纳入常规WES数据分析。结果显示,70例神经发育障碍儿童的WES检出率为30%(21/70)。在21例阳性病例中,14例检出单核苷酸变异/小插入缺失(SNV/Indel,其中有12个变异是未见文献报道的新变异),6例检出CNV,1例检出SNV和CNV的复合杂合变异。综合CNV分析的WES检出率高于单独的SNV/Indel分析(30%,21/70 vs.20%,14/70)。28例产前诊断病例中,6例检出遗传自NDDs父母的变异,10例未检出与先证者相同的致病变异,其余12例未检出可以解释NDDs表型的明确致病或疑似变异。随访显示5个家庭选择终止妊娠,其他目前暂无异常。综上,WES可能是明确NDDs患儿遗传病因和产前诊断的有效手段,有利于评估预后以辅助临床治疗和再生育指导。To explore the application value of whole exome sequencing(WES)in the diagnosis of prenatal and postnatal neurodevelopmental disorders(NDDs).A total of 70 patients diagnosed with NDDs who underwent WES at the Medical Genetics Center of the Maternal and Child Health Hospital of Hubei Province between June 2020 and July 2021 were retrospectively analyzed.Genomic DNA was extracted from peripheral blood samples and amniotic fluid.WES-based copy number variant(CNV)analysis was integrated into the routine WES data analysis pipeline.The results showed that a molecular diagnosis rate could be made in 21/70(30%)cases.Of 21 positive cases,14(23%)cases were detected by single-nucleotide variant/small insertion/deletion(SNV/Indel)analysis,of which 12 variants were novel,6(9.8%)cases were detected by WES-based CNV analysis,and 1(1.6%)case was detected by a combination of both.The diagnostic yield of WES combined with CNV analysis was higher than that of SNV/Indel analysis alone(30%,21/70 vs.20%,14/70).Of the 28 prenatally diagnosed cases,6 cases were found to have inherited parental variation for NDDs,10 cases were found not to have the same pathogenic variation as the proband,and the remaining 12 cases were found to have no pathogenic or likely pathogenic variation that could explain the NDDs phenotype.Clinical follow-up showed that 5 families opted for abortion and the remaining had no current abnormalities.In conclusion,WES may be an effective method to clarify the genetic etiology and prenatal diagnosis of NDDs,which is helpful in assessing the prognosis to aid clinical management and reproductive guidance.

关 键 词：神经发育障碍 外显子组测序 产前诊断 

分 类 号：R748[医药卫生—神经病学与精神病学]