biostudies-literatureUnknown14Gao SYBackground: Hereditary spastic paraplegia (HSP) is a progressive upper-motor neurodegenerative disease. Mutations in the WASHC5 gene are associated with autosomal dominant HSP, spastic paraplegia 8 (SPG8). However, due to the small number of reported cases, the exact mechanism remains unclear. Method: We report a Chinese family with HSP. The proband was referred to our hospital due to restless leg syndrome and insomnia. The preliminary clinical diagnosis of the proband was spastic paraplegia. Whole-exome sequencing (WES) and RNA splicing analysis were conducted to evaluate the genetic cause of the disease in this family. Results: A novel splice-altering variant (c.712-2A>G) in the WASHC5 gene was detected and further verified by RNA splicing analysis and Frontiers in genetics1205052https://www.ebi.ac.uk/biostudies/studies/S-EPMC10644772biostudies-literatureCase report: A novel WASHC5 variant altering mRNA splicing causes spastic paraplegia in a patient.PMC10644772Gao SYFan LLDong YLiu LLiu YXDing QfalseCase report: A novel WASHC5 variant altering mRNA splicing causes spastic paraplegia in a patient.Background: Hereditary spastic paraplegia (HSP) is a progressive upper-motor neurodegenerative disease. Mutations in the WASHC5 gene are associated with autosomal dominant HSP, spastic paraplegia 8 (SPG8). However, due to the small number of reported cases, the exact mechanism remains unclear. Method: We report a Chinese family with HSP. The proband was referred to our hospital due to restless leg syndrome and insomnia. The preliminary clinical diagnosis of the proband was spastic paraplegia. Whole-exome sequencing (WES) and RNA splicing analysis were conducted to evaluate the genetic cause of the disease in this family. Results: A novel splice-altering variant (c.712-2A>G) in the WASHC5 gene was detected and further verified by RNA splicing analysis and 2023-01-01T00:00:00Z20232026-05-16T03:17:50.155Z2025-02-19T01:16:25.233ZS-EPMC106447723802860810.3389/fgene.2023.1205052