一个罕见葡萄糖转运体1缺陷综合征家系的遗传学分析  

Genetic analysis of a family with rare glucose transporter 1 deficiency syndrome

作　　者：袁军鸿 段丽芬[3] 刘晓梅[4] 叶磊[5] 林克勤[2] 刘红仙 孙浩[2] 杨昭庆[2] YUAN Junhong;DUAN Lifen;LIU Xiaomei;YE Lei;LIN Keqin;LIU Hongxian;SUN Hao;YANG Zhaoqing(Kunming Medical University,Kunming,Yunnan 650500,China;Department of Medical Genetics,Institute of Medical Biology,Chinese Academy of Medical Sciences&Peking Union Medical College,Kunming,Yunnan 650118,China;Department of Neurology,Kunming Children's Hospital,Kunming,Yunnan 650034,China;Department of Infectious Diseases,Kunming Children's Hospital,Kunming,Yunnan 650034,China;Department of Neurosurgery,Kunming Children's Hospital,Kunming,Yunnan 650034,China)

机构地区：[1]昆明医科大学,云南昆明650500 [2]中国医学科学院/北京协和医学院医学生物学研究所医学遗传学研究室,云南昆明650118 [3]昆明市儿童医院神经内科,云南昆明650034 [4]昆明市儿童医院感染科,云南昆明650034 [5]昆明市儿童医院神经外科,云南昆明650034

出　　处：《中国优生与遗传杂志》2022年第12期2236-2240,共5页Chinese Journal of Birth Health & Heredity

基　　金：云南省应用基础研究项目(202001AY070001-273);云南省高层次卫生健康技术人才培养专项(L-2018003);昆明市卫生健康委员会卫生科研项目(2020-06-01-115)。

摘　　要：目的对一个罕见葡萄糖转运体1缺陷综合征(GLUT1-DS)家系的致病基因变异位点进行检测并对其进行遗传学分析。方法使用高通量全外显子组及PCR-Sanger检测家系成员的相关可疑突变位点,用I-TASSER生物信息学软件对含突变的蛋白质进行生物信息学分析,并采用PCR及毛细管电泳检测该核心家系成员中突变位点的嵌合比例。结果先证者在2月龄时发生首次抽搐,且具有容貌异常、脑脊液葡萄糖含量较低和脑电图异常等临床特征。先证者及其母亲在SLC2A1基因(NM_006516)检出杂合性无义突变c.988C>T(p.R330X),其母亲突变为新生突变(DNMs),但未产生明显的临床表型;蛋白结构生物信息分析表明p.R330X无义突变所产生的截短蛋白使SLC2A1基因编码的GLUT1蛋白丧失部分功能;嵌合体分析显示先证者及其母亲的嵌合率相近。结论该例GLUT1-DS患者的致病突变基因为SLC2A1基因c.988C>T无义突变,先证者母亲临床表型外显不全的原因可能是因为存在嵌合突变以外的分子病理机制。Objective To identify and genetically analyze pathogenic gene mutation in a rare family with glucose transporter 1 deficiency syndrome(GLUT1-DS).Methods High-throughput whole exome and PCR-Sanger were used to detect suspected mutations in family members.The bioinformatics analysis of the mutated protein was performed by I-TASSER bioinformatics software.PCR and capillary electrophoresis were used to detect the chimerism ratio of mutation sites in the core family members.Results The proband had the first convulsion at the age of 2 months,which was characterized by abnormal appearance,low glucose content in cerebrospinal fluid and abnormal electroencephalogram.Both proband and his mother were detected a heterozygous nonsense mutation c.988C>T(p.R330X)in the SLC2A1 gene(NM_006516),and this mutation was a de novo mutation for his mother,but the mother was asymptomatic.The protein structure analysis showed that the truncated protein produced by p.R330X nonsense mutation of SLC2A1 gene resulted in loss of partial function of GLUT1 protein.Chimerism analysis showed that the proportion of chimerism between the proband and his mother was similar.Conclusion The pathogenic gene mutation in the GLUT1-DS patient is SLC2A1 gene c.988C>T nonsense mutation,the clinical phenotype difference and incomplete penetrance of the proband’s mother might be resulted from genetic factors except mosaic SLC2A1gene.

关 键 词：GLUT1-DS SLC2A1基因 突变 表型异质性 嵌合体 

分 类 号：R725.9[医药卫生—儿科]