Abstract：
The objective of this study was to investigate the pathogenesis and inheritance pattern of a Chinese Han family with hereditary spastic paraplegia and to retrospectively analyze the characteristics of KIF1A gene variants and related clinical manifestations.
High-throughput whole-exome sequencing was performed on members of a Chinese Han family with a clinical diagnosis of hereditary spastic paraplegia, and the sequencing results were validated by Sanger sequencing. Deep high-throughput sequencing was performed on subjects with suspected mosaic variants. The previously reported pathogenic variant loci of the KIF1A gene with complete data were collected, and the clinical manifestations and characteristics of the pathogenic KIF1A gene variant were analyzed.
A pathogenic heterozygous variant located in the neck coil of the KIF1A gene (c.1139G>C, p.Arg380Pro) was identified in the proband and four additional members of the family. It was derived from the de novo low-frequency somatic-gonadal mosaicism of the proband\'s grandmother and had a rate of 10.95%.
This study helps us to better understand the pathogenic mode and characteristics of mosaic variants, and to understand the location and clinical characteristics of pathogenic variants in KIF1A.
High-throughput whole-exome sequencing was performed on members of a Chinese Han family with a clinical diagnosis of hereditary spastic paraplegia, and the sequencing results were validated by Sanger sequencing. Deep high-throughput sequencing was performed on subjects with suspected mosaic variants. The previously reported pathogenic variant loci of the KIF1A gene with complete data were collected, and the clinical manifestations and characteristics of the pathogenic KIF1A gene variant were analyzed.
A pathogenic heterozygous variant located in the neck coil of the KIF1A gene (c.1139G>C, p.Arg380Pro) was identified in the proband and four additional members of the family. It was derived from the de novo low-frequency somatic-gonadal mosaicism of the proband\'s grandmother and had a rate of 10.95%.
This study helps us to better understand the pathogenic mode and characteristics of mosaic variants, and to understand the location and clinical characteristics of pathogenic variants in KIF1A.
摘要：
目的：本研究的目的是探讨中国汉族家族遗传性痉挛性截瘫的发病机制和遗传模式，并回顾性分析KIF1A基因变异的特点及相关临床表现。
方法：对一个临床诊断为遗传性痉挛性截瘫的中国汉族家族成员进行了高通量全外显子组测序，测序结果经Sanger测序验证。对具有疑似镶嵌变体的受试者进行深度高通量测序。收集了先前报道的KIF1A基因的致病变异位点，并收集了完整的数据，并对致病性KIF1A基因变异的临床表现和特点进行分析。
结果：位于KIF1A基因颈部线圈中的致病性杂合变体（c.1139G>C，p.Arg380Pro）在先证者和该家族的另外四个成员中被确定。它源于先证者祖母的从头低频躯体性腺镶嵌性，发生率为10.95％。
结论：这项研究有助于我们更好地了解马赛克变体的致病模式和特征，了解KIF1A致病变异的部位和临床特点。
方法：对一个临床诊断为遗传性痉挛性截瘫的中国汉族家族成员进行了高通量全外显子组测序，测序结果经Sanger测序验证。对具有疑似镶嵌变体的受试者进行深度高通量测序。收集了先前报道的KIF1A基因的致病变异位点，并收集了完整的数据，并对致病性KIF1A基因变异的临床表现和特点进行分析。
结果：位于KIF1A基因颈部线圈中的致病性杂合变体（c.1139G>C，p.Arg380Pro）在先证者和该家族的另外四个成员中被确定。它源于先证者祖母的从头低频躯体性腺镶嵌性，发生率为10.95％。
结论：这项研究有助于我们更好地了解马赛克变体的致病模式和特征，了解KIF1A致病变异的部位和临床特点。
