【摘要】 目的分析和确诊2例16p11.2微缺失综合征患者及其家系成员的分子遗传学特征,探讨其基因型与临床表型的关系,为患者确诊和遗传咨询提供依据。方法收集2例患者及其家系成员的临床资料及外周血标本,应用全外显子测序结合全基因组低深度测序染色体拷贝数变异分析技术进行基因检测。结果 2例患者在16p11.2区域均存在约0.6 Mb缺失,该区域包含OMIM数据库中功能基因:ALDOA,CORO1A,KIFF22,PRRT2,TBX6等为致病性变异,从基因型和表型推测,相关疾病为16p11.2微缺失综合征,其变异分别来源于临床表型正常的(例1患者)父亲和(例2患者)母亲。结论通过基因型和临床表型分析,明确2个家系中患者均为16p11.2微缺失综合征,其基因型为致病性变异,但临床表型的严重程度存在异质性,可能与外显率密切相关。同时,运用全外显子测序技术可以显著提高表型变异较大的遗传学异常的检出率。更多还原

【Abstract】 Objective To analyze and insure the molecular genetic characteristics of 2 patients and their family members with the 16p11.2 microdeletion syndrome, and to explore the relationship between genotype and clinical feature phenotypes, thus providing a basis for diagnosis and genetic counseling regarding children.Methods The clinical data and peripheral blood samples of 2 patients and their family members were collected, and the whole exome sequencing(WES) technology and whole genome low-coverage sequencing for chromosome copy number variant sequencing(CNV-seq) were used for genetic testing. Results Both patients had a deletion of about 0.6 Mb in the 16p11.2 region, which contains functional genes in the OMIM database:ALDOA, CORO1 A, KIFF22, PRRT2 and TBX6, i.e. pathogenic variants. The related disease was 16p11.2 microdeletion syndrome. Analysis showed that the father of case 1 and the mother of case 2 had the same regional heterozygosity. Conclusion Through an analysis of genotype and clinical phenotype, the patient in the 2 families were of the 16p11.2 microdeletion syndrome. The genotype is was pathogenic variant, and the severity of the clinical phenotype was heterogeneous, and the penetrance was perhaps closely related; WES technology could greatly increase the detection rate of genetic diseases with substantial phenotypic variation.更多还原