一个新的TBR1基因剪接变异导致的智力障碍伴自闭症和语言障碍家系分析及产前诊断  

Identification of a novel TBR1 gene variant in a Chinese pedigree affected with intellectual developmental disorder with autism and speech delay

作　　者：曹旭[1] 李静 宋辉 朱媛媛 Cao Xu;Li Jing;Song Hui;Zhu Yuanyuan(Prenatal diagnosis center of WanBei Coal and Electricity Group General Hospital,Suzhou,Anhui 234000,China)

机构地区：[1]皖北煤电集团总医院产前诊断中心,宿州234000

出　　处：《中华医学遗传学杂志》2021年第10期933-936,共4页Chinese Journal of Medical Genetics

摘　　要：目的探讨1个由TBR1基因剪接变异导致的智力障碍伴自闭症和语言发育迟缓家系的临床特征及基因特点。方法对1例有家族史的智力障碍孕妇进行全外显子组检测,对先证者及其他家系成员(共11人)进行分子遗传学检测,发现该家系的致病位点,对胎儿羊水进行基因检测,并通过minigene技术对该位点进行体外功能验证。结果通过全外显子组测序发现,先证者携带1个TBR1基因新的剪接变异(c.1129-1G>C),并呈现出家系共分离现象。胎儿羊水中未发现该变异,胎儿出生后随访至1岁,智力运动发育正常。Minigene结果显示第5外显子出现异常剪接。结论TBR1基因c.1129-1G>C变异可能是该家系的致病原因,及时的产前遗传诊断和咨询有助于阻断致病基因在家系中的传递。Objective To describe a family with intellectual developmental disorder with autism and speech delay(IDDAS)caused by a splice variant ofTBR1 gene.Methods A pregnant women with mental retardation,who also had a family history of mental retardation,was admitted to Prenatal Diagnosis Center of WanBei Coal and Electricity Group General Hospital Corporation in April 2019.Molecular genetic tests were performed on the pregnant women and ten other family members to analyze the pathogenic genotype.Functional assays of the pathogenic variant was carried out by minigene technology.With the determination of the genotype,prenatal diagnosis was carried out by amniotic fluid sampling.Results Through whole exome sequencing,a novel splicing variant(c.1129-1G>C)was identified in the TBR1 gene of the proband,which has co-segregated with the disease phenotype in the family.The results of minigene assay showed abnormal splicing of exon 5.The variant was not detected in the fetal amniotic fluid.Fetal growth and development were normal one year after the birth.Conclusion The c.1129-1G>C variant of theTBR1 probably underlay the disease in of the pedigree.Timely prenatal genetic diagnosis and consultation can help to stop the transmission of the pathogenic variant.

关 键 词：TBR1基因 智力障碍伴自闭症和语言发育迟缓 剪接变异 

分 类 号：R749.94[医药卫生—神经病学与精神病学]