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

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.

This is the peer reviewed version of the following article: Y. Nakano, Y. Fukui, K. Deguchi, et al., “ A Case of Retinopathy–Sensory Neuropathy Syndrome With a Novel Compound Heterozygous FLVCR1 Variant,” Journal of the Peripheral Nervous System 30, no. 4 (2025): e70082, https://doi.org/10.1111/jns.70082., which has been published in final form at https://doi.org/10.1111/jns.70082. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.

This is an Accepted Manuscript of an article published by Dec. 2026.