[FA2H gene-associated spastic paraplegia (SPG35) - familial case with late onset].

Abstract

Autosomal recessive spastic paraplegia type 35 (SPG35), associated with the FA2H gene, is characterized by onset in childhood (usually at 3-5 years) and a «complicated» phenotype: signs associated with spastic paraparesis and MRI changes. We describe a very rare case of late-onset SPG35 with differences in sisters aged 47 and 45 in a non-inbred Russian family. Spastic paraparesis in the older sister manifested at the age of 40 and in the younger sister-at the age of 25; cognitive-personal disorders manifested at the age of 42 and 40, respectively, and rapidly progressed; both developed dysarthria. MRI in both sisters showed periventricular leukopathy (more pronounced in the older one), atrophic changes in the cortex and cerebellum (more pronounced in the younger one) and hypointensity in the area of pale globes, and thinning of the corpus callosum (only in the younger sister). Whole genome sequencing (WGS) followed by family Sanger sequencing for the sisters showed the previously described missense variants c.232G>A, p.Glu78Lys and c.137G>A, p.Gly46Asp in the FA2H gene in a compound-heterozygous state; the mother had a heterozygous variant of p.Glu78Lys (the father died, there are no other siblings). This article is a literature review on the late-onset SPG35.