Novel Bi-Allelic Variants in RINT1 Presenting As Early-Onset Pure Hereditary Spastic Paraplegia

The hereditary spastics paraplegias (HSPs) are a group of over 80 neurogenetic disorders that share the feature of progressive lower limb spasticity. Bi-allelic loss-of-function variants in the RINT1 gene have been implicated in acute liver failure in the pediatric population, and were recently described to lead to a complex form of HSP in three children with early-onset spastic paraplegia, ataxia, optic nerve hypoplasia with significant vision impairment, dysmorphic features, and a thin corpus callosum. We read the article by Launay et al. with great interest and would like to add a fourth case due to novel biallelic RINT1 variants presenting with a largely 'pure' form of HSP including one missense variant and one splice site variant identifier by whole genome sequencing. Overall design: To investigate the impact of the splice site variant, we conducted a skin biopsy and created a fibroblast cell line. RNA sequencing was performed.