痉挛性截瘫30型一个家系的KIF1A基因变异分析

Analysis of KIF1A gene variant in a Chinese pedigree affected with Spastic paraplegia type 30

目的探讨1例遗传性痉挛性截瘫30型(HSP30)家系的遗传学病因。方法以2021年8月就诊于山西医科大学第二医院的1例先证者以及家系成员为研究对象,对其进行全外显子组测序,并对候选变异进行Sanger测序家系验证。结果先证者携带KIF1A基因第3外显子c.110T>C(p.I37T)杂合变异,造成第37位的异亮氨酸替换为苏氨酸,可能影响其蛋白质产物的功能。先证者的父母、哥哥和姐姐均未携带相同的变异,提示其为新发变异。根据美国医学遗传学与基因组学学会(ACMG)相关指南,判断该变异为可能致病性变异(PM2_Supporting+PP3+PS2)。结论KIF1A基因c.110T>C变异可能是该先证者的遗传学病因。

Objective To explore the genetic basis for a Chinese pedigree affected with hereditary spastic paraplegia type 30(HSP30).Methods A proband presented at the Second Hospital of Shanxi Medical University in August 2021 was selected as the study subject.The proband was subjected to whole exome sequencing,and candidate variant was verified by Sanger sequencing and bioinformatic analysis.Results The proband was found to have harbored a heterozygous c.110T>C variant in exon 3 of the KIF1A gene,which can cause substitution of isoleucine by threonine at position 37(p.I37T)and alter the function of its protein product.The same variant was not found in his parents,elder brother and elder sister,suggesting that it has a de novo origin.Based on the guidelines of the American College of Medical Genetics and Genomics(ACMG),the variant was rated as likely pathogenic(PM2_Supporting+PP3+PS2).Conclusion The c.110T>C variant of the KIF1A gene probably underlay the HSP30 in the proband.Above finding has enable genetic counseling for this family.