A Case of Retinopathy–Sensory Neuropathy Syndrome With a Novel Compound Heterozygous FLVCR1 Variant

ABSTRACT Background and Aims Retinopathy–sensory neuropathy syndrome (RETSNS), also known as posterior column ataxia with retinitis pigmentosa (PCARP), is a rare neurodegenerative disorder that is caused by biallelic pathogenic variants in FLVCR1 . Here, we report a case of a Japanese patient with RETSNS. Methods Clinical, neuroradiological, and electrophysiological findings were documented. Whole‐genome sequencing was performed. Subcloning was carried out to confirm compound heterozygosity. A functional assay was performed to assess the pathogenicity of the variants. Results The patient showed retinitis pigmentosa and sensory ataxia. Over the course of the disease, autonomic dysfunction has become increasingly evident. Despite consanguinity in the family, whole‐genome sequencing identified two heterozygous variants in FLVCR1 (c.369T>G, p.Phe123Leu and c.733A>G, p.Asn245Asp). Cloning of the PCR product followed by Sanger sequencing indicated compound heterozygosity of the variants. Immunocytochemistry of HEK293FT cells transfected with plasmids containing wild‐type or variant FLVCR1 cDNA demonstrated altered subcellular localization of the variant FLVCR1 proteins, characterized by reduced membrane localization. Interpretation We report a novel variant in FLVCR1 causing RETSNS. The functional assay supports the pathogenicity of the variants.