TUBB基因p.M73V变异所致复合型脑皮质发育不良伴其他脑发育畸形6型患儿1例的遗传学分析  

Genetic analysis of a child with Complex cortical dysplasia with other brain malformations type 6 due to a p.M73V variant of TUBB gene

作　　者：薛慧琴 唐巧茵 郭荣 曹桂芝 冯宇 孙夏瑜 卢洪涌 Xue Huiqin;Tang Qiaoyin;Guo Rong;Cao Guizhi;Feng Yu;Sun Xiayu;Lu Hongyong(Shanxi Provincial Children′s Hospital(Shanxi Provincial Maternal and Child Health Care Hospital),Taiyuan,Shanxi 030013,China;Pediatrics Discipline,Graduate School of Shanxi Medical University,Taiyuan,Shanxi 030001,China)

机构地区：[1]山西省儿童医院(山西省妇幼保健院)细胞遗传室,太原030013 [2]山西医科大学研究生学院儿科医学系,太原030013

出　　处：《中华医学遗传学杂志》2023年第12期1541-1545,共5页Chinese Journal of Medical Genetics

基　　金：山西省回国留学人员科研资助项目(20171702);山西省留学人员科技活动择优资助项目(201919);"十三五"国家科技计划国家人口与生殖健康科学数据共享服务平台子课题(SJPT-03-16)。

摘　　要：目的探讨1例多发畸形患儿的遗传学病因。方法以2021年2月就诊于山西省儿童医院的1例患儿作为研究对象。收集患儿的临床信息,并对其进行全外显子组测序(WES),对候选变异进行Sanger测序家系验证以及致病性分析。结果患儿全身皮肤无异常,但存在右耳缺如、半椎体畸形,心室间隔缺损、动脉导管与卵圆孔未闭、左肾集合系统分离等。磁共振成像显示双侧侧脑室不规则增大、大脑皮层与颞侧脑膜间距增加。测序发现其携带TUBB基因NM_178014.4:c.217A>G(p.Met73Val)新发杂合变异,根据美国医学遗传学与基因组学学会(ACMG)相关指南判定为可能致病。结合其临床表型以及基因检测结果,患儿被确诊为复合型脑皮质发育不良伴其他脑发育畸形6型(CDCBM6)。结论CDCBM是一类罕见的具有遗传异质性的严重疾病,其中TUBB基因缺陷所致的CDCBM6更为罕见。本研究的结果扩展了TUBB基因的变异谱和表型谱,为总结CDCBM6的基因型-表型对应关系提供了重要的参考。Objective To explore the genetic basis for a child with multiple malformations.Methods A child who had presented at Shanxi Provincial Children′s Hospital in February 2021 was selected as the study subject.Clinical data of the patient was collected,and whole exome sequencing(WES)was carried out to screen pathogenic variants associated with the phenotype.Candidate variant was validated by Sanger sequencing of her family members.Results The child had normal skin,but right ear defect,hemivertebral deformity,ventricular septal defect,arterial duct and patent foramen ovale,and separation of collecting system of the left kidney.Cranial MRI showed irregular enlargement of bilateral ventricles and widening of the distance between the cerebral cortex and temporal meninges.Genetic testing revealed that she has harbored a heterozygous variant of NM_178014.4:c.217A>G(p.Met73Val)in the TUBB gene,which was unreported previously and predicted to be likely pathogenic based on the guidelines from the American College of Medical Genetics and Genomics(ACMG).The child was diagnosed with Complex cortical dysplasia with other brain malformations 6(CDCBM6).Conclusion CDCBM is a rare and serious disease with great genetic heterogeneity,and CDCBM6 caused by mutations of the TUBB gene is even rarer.Above finding has enriched the variant and phenotypic spectrum of the TUBB gene,and provided important reference for summarizing the genotype-phenotype correlation of the CDCBM6.

关 键 词：TUBB基因 复合型脑皮质发育不良伴其他脑发育畸形 先天性对称皮肤褶皱综合征 

分 类 号：R742[医药卫生—神经病学与精神病学]