Novel heterozygous UCHL1 variant causing severe optic atrophy and vision loss

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

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

Genetic testing revealed a novel pathogenic UCHL1 variant accounting for the two individuals' phenotype.

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.