Phenotypic spectrum of autosomal recessive retinitis pigmentosa without posterior column ataxia caused by mutations in the FLVCR1 gene.

PURPOSE: Posterior column ataxia and retinitis pigmentosa (PCARP) is a rare form of syndromic RP associated with mutations in the FLVCR1 gene. Recent evidence has suggested a spectrum in the phenotype depending on the genotype.

METHODS: Six individuals with retinitis pigmentosa (RP) carrying mutations in the FLVCR1 gene underwent detailed ophthalmological examinations at the Center for Ophthalmology and two of these also an extensive neurological examination at the Department of Neurology in Tuebingen, Germany.

RESULTS: The mutation spectrum in our cohort comprised one nonsense mutation, one 1-bp deletion, two missense variants, and one splice site variant (c.1092+5G>A). Three patients presented with a typical clinical picture of autosomal recessive RP, two patients presented with atypical RP, and one patient presented with a particularly mild form of RP. The findings of the patients that underwent detailed neurological and neurophysiological testing were not suggestive for the presence of progressive PCA, but one patient showed mild cerebellar signs without worsening over time. Five out of six of our cases carry the splice site variant c.1092+5G>A at least on one allele possibly providing evidence as to that this splice site variant may cause a milder form of non-syndromic autosomal recessive RP.

CONCLUSIONS: Mutations in FLVCR1 can present with the clinical picture of a non-syndromic autosomal recessive RP (in this case RP without PCA), RP with mild cerebellar signs, but also PCARP. Additionally, we show evidence for a spectrum of the severity of the retinal involvement likely depending on the genotype.