TUBA1A基因新发变异患儿的临床特征及遗传学分析  

Clinical characteristics and genetic analysis of a child with a new mutation of TUBA1A gene

作　　者：李成林 魏娜 杨礼 刘奇迹 谭冰玲 周林 付佳 朱龙云 崔迪 孙雪晶 Li Chenglin;Wei Na;Yang Li;Liu Qiji;Tan Bingling;Zhou Lin;Fu Jia;Zhu Longyun;Cui Di;Sun Xuejing(Department of Rehabilitation,Dongchangfu Maternal and Child Health Hospital,Liaocheng 252000,China;Medical Genetics Laboratory,Dongchangfu District Maternal and Child Health Hospital,Liaocheng 252000,China;Key Laboratory for Experimental Teratology of the Education and Department of Medical Genetics Shandong Univercitiy School of the Basic Medical Sciences,Jinan 250012,China;Department of Translational Medicine Center,Chigene(Beijing)Translational Medical Research Center Co.,Beijing 100176,China)

机构地区：[1]聊城市东昌府区妇幼保健院康复科,聊城252000 [2]聊城市东昌府区妇幼保健院检验科,聊城252000 [3]山东大学基础医学院实验畸形学教育部重点实验室与医学遗传系,济南250012 [4]北京智因东方转化医学研究中心有限公司,北京100176

出　　处：《国际遗传学杂志》2024年第4期278-283,共6页International Journal of Genetics

基　　金：山东省医药卫生科研发展计划课题(2017WS014)。

摘　　要：目的分析1例全面性发育迟缓、多次抽搐患儿的遗传学病因及影像学特征。方法对在聊城市东昌府区妇幼保健院遗传康复科就诊的1例全面发育迟缓、多次抽搐的患儿运用全外显子测序技术和脑功能成像技术探讨其致病原因,分析其临床表型、影像学特征及遗传学特点。结果全外显子测序结果显示患儿携带TUBA1A基因c.518C>T(p.P173L)杂合变异,该突变在其临床表型正常的父母中未检测到,为新发突变。颅脑MRI结果显示胼胝体发育略薄,脑沟和脑回未见明显异常,进一步行脑功能成像检查发现胼胝体体部小部分纤维束显示稀疏,左侧毯部纤维较右侧稀疏,右侧额枕下束较左侧明显稀疏,双侧弓状纤维额颞部稀疏,结果提示大脑发育和部分脑功能区受损。结论本研究采用全外显子测序技术发现1例TUBA1A基因c.518C>T(p.P173L)的杂合变异患者,通过磁共振脑功能成像(functional magenetic resonance imaging,fMRI)发现患儿大脑功能发育和部分脑功能区受损,补充了TUBA1A基因致病的临床表型数据库。ObjectiveTo analyze the genetic etiology and imaging features of a child with generalized developmental delay and multiple seizures.MethodsThe whole exon sequencing technology and brain functional imaging technology were used to explore the cause of a child with global developmental delay and multiple convulsions in the Department of Genetic Rehabilitation of our hospital,and the clinical phenotype,imaging characteristics and genetic characteristics were analyzed.ResultsWhole exome sequencing results showed that the patient carried a heterozygous de novo variant of c.518C>T(p.P173L)in the TUBA1A gene.The mutation was not detected in his parents with normal clinical phenotype,which was a new mutation.Brain MRI results showed that the development of corpus callosum was slightly thinner,and there was no obvious abnormality in the sulci and gyri.Further brain functional imaging examination showed that a small part of the corpus callosum fiber bundle was sparse,the left carpet fiber was sparser than the right side,the right fronto-occipital bundle was significantly sparser than the left side,and the bilateral arcuate fibers were sparse in the frontal and temporal regions.The results suggest that brain development and some brain functional areas are impaired.ConclusionWe found a patient with a heterozygous de novo variant of TUBA1A gene c.518C>T(p.P173L)by whole exome sequencing.The brain function development and some brain functional areas were damaged by fMRI,which supplemented the clinical phenotype database of TUBA1A gene.

关 键 词：全外显子测序 无脑回-巨脑回畸形3型 TUBA1A FMRI 

分 类 号：R725.9[医药卫生—儿科]