A cone‐rod dystrophy patient with a homozygous RP1L1 mutation

Abstract

AbstractPurpose To describe a family with a cone‐rod dystrophy patient who has homozygous mutation of the RP1‐like protein 1 (RP1L1) gene.Methods A family including a cone‐rod dystrophy patient underwent detailed ophthalmic clinical evaluations including high resolution cone photorecepor imaging with adaptive optics fundus camera. Mutation screening of the sequence of RP1L1 gene were performed by DNA sequencing analysis in this family membersResults A patient showed a mild reduction of cone and flicker response in full‐field electroretinogram (ERG). Her ERG also showed slight decrease in the amplitude of rod response. IS/OS junction and COST line in SD‐OCT images are severely disturbed. Response of multifocal ERGs (mfERGs) of the patient was severely reduced. A homozygous RP1L1 mutation (c.3628 T>C) was identified in the patient. The mutation c.3628 T>C in exon 4 resulted in the substitution of proline for serine at amino acid position 1210. This mutation was not reported in SNP database. The serine at position 1210 is well conserved among the RP1L1 family in other species. Four out of five computational assessment tools predicted that this mutation is damaging to the protein function. This mutation was not present in 460 control alleles. Family members with heterozygous S1210P mutation showed normal best‐corrected visual acuity (BCVA), SD‐OCT, mfERGs, and focal macular ERGs. Adaptive Optics (AO) images of the patient showed severe reduction of cone density and irregular cone mosaic despite family members with heterozygous S1210P mutation showed normal cone density and regular cone mosaic.Conclusion We have demonstrated a possibility that autosomal recessive cone‐rod dystrophy may be caused by homozygous RP1L1 mutation.