一例复杂性皮质发育异常伴其他脑部畸形胎儿的TUBB2B基因变异分析  

Analysis of TUBB2B gene variant in a fetus with complex cortical dysplasia with other brain malformations-7

作　　者：闫露露[1] 卢寨娥[2] 刘颖文 韩春晓 应红军[2] 鲍幼维 薛江阳 李海波 Yan Lulu;Lu Zhaier;Liu Yingwen;Han Chunxiao;Ying Hongjun;Bao Youwei;Xue Jiangyang;Li Haibo(The Central Laboratory for Birth Defect Prevention and Control,Ningbo Women and Children’s Hospital Zhejiang 315012,China;Department of Obstetrics,Ningbo Women and Children’s Hospital,Zhejiang 315012,China)

机构地区：[1]宁波市妇女儿童医院出生缺陷综合防治中心,浙江315012 [2]宁波市妇女儿童医院产科,浙江315012

出　　处：《中华医学遗传学杂志》2022年第3期301-304,共4页Chinese Journal of Medical Genetics

基　　金：宁波市社会发展公益领域基金(2019C50070);浙江省医药卫生计划(2020KY889,2020KY890);宁波市科技计划(202002N3150,2014B82003)。

摘　　要：目的对一例胼胝体发育不全并伴有其他脑部畸形的胎儿进行遗传学分析,以明确其致病原因。方法应用全外显子组测序(whole exome sequencing,WES)技术筛选与胎儿表型相符合的致病变异,并对先证者及其父母进行Sanger测序验证。结果WES发现胎儿TUBB2B基因第4外显子存在一处新发错义变异c.758T>A(p.L253Q),既往未见报道。根据美国医学遗传学与基因组学学会遗传变异分类标准与指南,TUBB2B基因c.758T>A为可能致病性变异。生物信息学分析提示TUBB2B蛋白第253位亮氨酸在多个物种中高度保守,c.758T>A变异可能影响Leu253、Asp249和Met257残基之间氢键的形成,影响GTP/GDP的结合,最终影响蛋白的功能。结论TUBB2B基因c.758T>A(p.L253Q)杂合变异可能是导致胎儿脑部畸形的原因。上述发现拓展了TUBB2B基因的变异谱,为该家系的遗传咨询和产前诊断提供了依据。Objective To explore the genetic basis for a fetus with dysgenesis of corpus callosum and other brain malformations.Methods Whole exome sequencing was carried out for the fetus and its parents.Suspected pathogenic variants were verified by Sanger sequencing.Results A novel de novo missense variant c.758T>A(p.L253Q)of the TUBB2B gene was identified,which was unreported previously.Based on the guidelines from the American College of Medical Genetics,the c.758T>A variant was predicted to be likely pathogenic.Bioinformatics analysis predicted that the leucine at position 253 was highly conserved among various species,and the c.758T>A variant may impact the formation of hydrogen bonds between Leu253 and Asp249 and Met257 residues,which in turn may affect the combination of GTP/GDP and function of the TUBB2B protein.Conclusion The c.758T>A variant of the TUBB2B gene probably underlay the fetal malformations in this Chinese family.Above discovery has enriched the spectrum of TUBB2B gene variants and provided a basis for genetic counseling and prenatal diagnosis.

关 键 词：颅脑畸形 TUBB2B基因 全外显子组测序 

分 类 号：R714.5[医药卫生—妇产科学]