CNV-seq在先天性唇腭裂患者中的临床应用  

Clinical application of CNV-seq in patients with congenital cleft lip and palate

作　　者：肖艳华 时盼来 王爱玲 王建红 李瑞 张欣 庞新丰 李鼎 张楚 孔祥东 Xiao Yanhua;Shi Panlai;Wang Ailing;Wang Jianhong;Li Rui;Zhang Xin;Pang Xinfeng;Li Ding;Zhang Chu;Kong Xiangdong(Medical Genetics and Prenatal Diagnosis Center,Jiaozuo Maternal and Child Health Care Hospital(Key Medical Laboratory of Prenatal Diagnostic in JiaoZuo),Jiaozuo 454000,China;Genetics and Prenatal Diagnosis Center,First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China;Neurology Department,People’s Hospital of Jiaozuo,Jiaozuo 454000,China)

机构地区：[1]河南省焦作市妇幼保健院遗传与产前诊断中心(焦作市产前诊断医学重点实验室),焦作454000 [2]郑州大学第一附属医院遗传与产前诊断中心,郑州450052 [3]河南省焦作市人民医院神经内科,焦作454000

出　　处：《国际遗传学杂志》2022年第5期361-367,共7页International Journal of Genetics

基　　金：2019年度河南省医学科技公关计划联合共建项目(LHGJ20191365);国家重点研发计划子课题(2018YFC1002206-2)。

摘　　要：目的探讨先天性唇腭裂与染色体拷贝数变异(copy number variation,CNVs)的关系及筛选可疑候选基因。方法采用拷贝数变异测序(CNV sequencing,CNV-seq)技术对先天性唇腭裂外周血或羊水标本进行全基因组CNVs检测。结果42例样本检测成功率100%,共检出5例致病性CNVs(11.9%),均发生在综合征型唇腭裂(22.7%,5/22),非综合征型唇腭裂未检出致病性CNVs(0,0/20),差异具有统计学意义(P=0.023)。本研究共检出7个致病性CNVs,分别为14q32.31q32.33微缺失、18q21.31q23微缺失、4p16.3p14微缺失、18q22.1q23微重复、5p15.33微缺失、9p24.3p13.2微重复和17q12微缺失。在检出的致病性CNVs区间,共筛选出5个可能与唇腭裂相关的可疑候选基因,分别为BRF1、TXNL4A、FGFR3、NSD2和BNC2。结论先天性唇腭裂的发生与染色体CNV密切相关,本研究发现5个可能与唇腭裂相关的候选基因。Objective To explore the relationship between congenital cleft lip and/or palate and copy number variations and to screen suspicious candidate genes.Methods Copy number variations(CNVs)of the congenital cleft lip and/or palate specimens were detected by CNV sequencing(CNV-seq).Results 42(100%)specimens were analyzed successfully,and 5(11.9%)of them were diagnosed with pathogenic CNVs.The 5 pathogenic CNVs all happened in syndromic cleft lip or palate(22.7%,5/22),and no pathogenic CNVs were detected in non-syndromic cleft lip or palate(0,0/20).The difference was statistically significant(P=0.023).7 pathogenic CNVs were detected in this study,including 14q32.31q32.33 microdeletion,18q21.31q23 microdeletion,4p16.3p14 microdeletion,18q22.1-q23 microduplication,5p15.33 microdeletion,9p24.3-p13.2 microduplication and 17q12 microdeletion.5 suspicious candidate genes related to cleft lip and/or palate were screened in the range of these pathogenic CNVs,containing BRF1、TXNL4A、FGFR3、NSD2 and BNC2.Conclusion The congenital cleft lip and/or palate is closely related to CNVs.We found 5 candidate genes related to cleft lip and/or palate in this stduy.

关 键 词：先天性唇腭裂 拷贝数变异 拷贝数变异测序 可疑候选基因 

分 类 号：R782.2[医药卫生—口腔医学]