Objective: 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.
Methods: 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.
Results: 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%.
Interpretation: 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.
Keywords: KIF1A; deep high-throughput sequencing; hereditary spastic paraplegia; mosaic variant.
© 2023 John Wiley & Sons Ltd/University College London.