Novel variant in Moroccan patient with hereditary spastic paraplegia type 35

Abstract

Hereditary Spastic Paraplegia Type 35 (HSP35) is a complex form of Hereditary Spastic Paraplegia. The main features of HSP35 include progressive paraparesis, dysarthria, and mild cognitive decline, along with the presence of leukodystrphy on brain imaging. HSP35 is caused by pathogenic variants in the fatty acid 2-hydroxylase protein (FA2H).In this study, whole exome sequencing (WES) was performed on a Moroccan family displaying HSP features. The genetic analysis revealed the novel variant (p.Thr352Pro) in the FA2H in the HSP in the family affected by HSP35. Computational analysis demonstrated a reduction in protein stability and alterations in amino acid interactions in the FA2H protein associated with p.Thr352Pro variant. Our study provides more insight about HSP35 associated variants, which can be valuable for counseling patients with HSP. Additionally molecular biology studies are required to investigate the genotype-phenotype correlation of FA2H- associated HSPs.