一个葡萄糖转运体1缺乏综合征家系的临床表型及SLC2A1基因变异分析

Analysis of clinical phenotype and variant of SLC2A1 gene in a Chinese pedigree affected with glucose transporter 1 deficiency syndrome

目的分析一个葡萄糖转运体1缺乏综合征(glucose transporter type 1 deficiency syndrome,GLUT1-DS)家系的临床表型,并对其SLC2A1基因进行变异检测和遗传特征分析。方法收集1例因运动语言发育落后就诊患儿及其家庭成员的临床资料,并采集外周血样,提取DNA,进行医学全外显子高通量测序分析,并对其父母和姐姐进行Sanger测序验证,确定变异位点,分析其与表型的对应关系。结果患儿及母亲、姐姐有共同的临床表现,包括智力运动发育落后、运动耐受差、易疲劳、阵发性肌张力障碍;不同的是患儿及母亲存在小头畸形、癫痫发作,而姐姐无此表现。家系中患病者均存在SLC2A1 c.191T>C(p.L64P)变异位点,1号染色体43396801位置发生了杂合错义变异,既往未见报道。结论患儿及其母亲、姐姐所具有的SLC2A1 c.191T>C(p.L64P)杂合错义变异,是造成语言运动发育落后、癫痫发作及阵发性肌张力障碍、智力低下等的原因。共同的SLC2A1基因变异位点,临床表型却不尽相同,反映了GLUT1-DS的遗传和表型多样性。新的基因变异位点的检出丰富了GLUT1-DS基因的变异谱。

Objective To analyze the clinical phenotype and variant of SLC2A1 gene in a Chinese pedigree affected with glucose transporter type 1 deficiency syndrome(GLUT1-DS).Methods Clinical data of a child who was treated due to delayed motor and language development and his family members were collected.DNA was extracted from peripheral blood samples and subjected to high-throughput medical exome sequencing.Candidate variant was verified by Sanger sequencing of his parents and sister.The genotype-phenotype correlation was explored.Results The child,his mother and sister had common manifestations such as delayed mental and motor development,poor exercise tolerance,easy fatigue and paroxysmal dystonia,but the difference was that the child and his mother had microcephaly and seizures,while his sister did not.A heterozygous missense SLC2A1 c.191T>C(p.L64P)variant was identified in all affected members,which was unreported previously.Conclusion The missense SLC2A1 c.191T>C(p.L64P)variant probably underlay the disease in the proband and his mother and sister.Variability of the clinical phenotypes has reflected the genetic and phenotypic diversity of GLUT1-DS.Detection of the novel variant has enriched the spectrum of GLUT1-DS mutations.