两例CHARGE综合征患儿的基因突变分析

摘要

Objective To analyze two Chinese pediatric patients with multiple malformations and growth and development delay.Methods Both patients were subjected to targeted gene sequencing,and the results were analyzed with Ingenuity(R) Variant AnalysisTM software.Suspected pathogenic variations were verified by Sanger sequencing.Results High-throughput sequencing showed that both patients have carried heterozygous variants of the CHD7 gene.Patient 1 carried a nonsense mutation in exon 36 (c.7957C＞T,p.Arg2653 *),while patient 2 carried a nonsense mutation of exon 2 (c.718C＞T,p.Gln240 *).Sanger sequencing confirmed the above mutations in both patients,while their parents were of wild-type for the corresponding sites,indicating that the two mutations have happened de novo.Conclusion Two patients were diagnosed with CHARGE syndrome by high-throughput sequencing.%目的 分析2例分别表现为多发畸形和生长发育迟缓患儿的遗传学原因.方法 应用靶向基因测序技术对2例患儿的外周血基因组DNA进行高通量测序,用Ingenuity变异分析软件对测序结果进行分析,同时对检出的致病性变异位点进行Sanger测序验证.结果 高通量测序结果显示例1的CHD7基因的第36外显子存在c.7957C＞T(p.Arg2653*)无义突变;例2的CHD7基因第2外显子存在c.718C＞T (p.Gln240*)无义突变.Sanger测序结果验证了两例患儿CHD7基因的突变,患儿的父母均未检测到突变,患儿CHD7基因的突变均为新生突变(de novo).结论 CHD7基因突变是两例患儿的遗传学病因.