三例22q13缺失综合征患儿的临床及遗传学分析

Clinical and genetic analysis of three children with 22q13 deletion syndrome

目的探讨3例22q13缺失综合征患儿的临床及遗传学特点,为其家系的遗传咨询和产前诊断提供依据。方法收集患儿及家系的临床资料,采集其外周血样,进行比较基因组杂交(array-based comparative genomic hybridization,aCGH)与基因组拷贝数变异测序(copy number variation sequencing,CNV-Seq)检测,检索DECIPHER、ClinGen、OMIM、PubMed、GeneReview等数据库,分析CNV变异的致病性。结果3例患儿均具有不同程度的发育落后,其中语言落后较为明显。患儿1头颅磁共振成像显示胼胝体异常;患儿2发育落后最为严重,同时伴有牙齿差、肤白、手掌厚等特征,且肌张力低;患儿3症状最轻。患儿幼时语言功能落后显著,追赶发育后明显改善。3例患儿均发现仅在染色体22q13.33q13.33区存在缺失。患儿1缺失0.84 Mb,涉及37个基因;患儿2缺失8.70 Mb,涉及126个基因;患儿3缺失0.90 Mb,涉及34个基因。对3例患儿的父母相应CNV变异区域进行检测结果均发现异常。结论丰富了22q13缺失综合征的临床及遗传学特征,为后续的遗传咨询及产前诊断提供了依据。

Objective To explore the clinical and genetic characteristics of three children with 22q13 deletion syndrome..Methods Clinical data were collected and copy number variations in the patients and their parents were detected by using array-based comparative genomic hybridization(aCGH)and copy number variation sequencing(CNV-seq).The DECIPHER,ClinGen,OMIM,PubMed and Gene Review databases were retrieved for pathogenicity analysis..Results The common phenotypes of the three children have included variable global developmental delay,among which speech delay was the most obvious.Patient 1 had abnormalities of corpus callosum shown by magnetic resonance imaging.Patient 2 had dental crowding,pale skin,thick palms,hypotonia,and other facial features.Patient 3 had the mildest symptoms including language dysfunction,which has caught up with the development and improved significantly.All of the three children had harbored de novo deletions of 22q13.33q13.33 region,which spanned 0.84 Mb,8.70 Mb and 0.90Mb and involved 37,126,and 34 genes,respectively.Conclusion Above finding has enriched the clinical and genetic characteristics of 22q13 deletion syndrome and laid a foundation for genetic counseling and prenatal diagnosis.