Novel heterozygous UCHL1 variant causing severe optic atrophy and vision loss

Ophthalmic Genet. 2026 Apr 9:1-4. doi: 10.1080/13816810.2026.2655887. Online ahead of print.

ABSTRACT

INTRODUCTION: Heterozygous UCHL1 variants have recently been associated with an autosomal dominant neurodegenerative disease characterized by spastic ataxia, optic atrophy and neuropathy.

METHODS: We describe two individuals from a single family who presented with optic atrophy and progressive vision loss, without demonstrable spasticity, ataxia or peripheral neuropathy.

RESULTS: Genetic testing revealed a novel pathogenic UCHL1 variant accounting for the two individuals’ phenotype.

DISCUSSION: Our findings highlight the significant phenotypic variability related to heterozygous UCHL1-related disease. Clinicians should consider UCHL1 variants in individuals presenting with multigenerational optic atrophy even in the absence of multisystem features.

PMID:41958053 | DOI:10.1080/13816810.2026.2655887