[一个中国遗传性痉挛性截瘫30型家系中KIF1A基因变异的分析]
[Analysis of KIF1A gene variant in a Chinese pedigree affected with Spastic paraplegia type 30].
作者信息
Xu Gang, Li Jianwei, Deng Zhanjin, Xia Yuan, Wang Tao, Bai Yan, Qi Yan, Zhou Yong An
机构信息
The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, China.
出版信息
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2023 Apr 10;40(4):419-422. doi: 10.3760/cma.j.cn511374-20220718-00475.
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.
目的
探究一个患有30型遗传性痉挛性截瘫（HSP30）的中国家系的遗传基础。
方法
选取2021年8月在山西医科大学第二医院就诊的一名先证者作为研究对象。对该先证者进行全外显子组测序，并通过Sanger测序和生物信息学分析验证候选变异。
结果
发现该先证者的KIF1A基因外显子3存在杂合的c.110T>C变异，该变异可导致第37位的异亮氨酸被苏氨酸替代（p.I37T），并改变其蛋白质产物的功能。在其父母、哥哥和姐姐中未发现相同变异，提示该变异为新发突变。根据美国医学遗传学与基因组学学会（ACMG）的指南，该变异被评为可能致病（PM2_Supporting+PP3+PS2）。
结论
KIF1A基因的c.110T>C变异可能是该先证者HSP30的致病原因。上述发现为该家庭提供了遗传咨询依据。
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