Recessive pediatric-onset cone-rod dysfunction or dominant maculopathy in a consanguineous family harboring the peripherin mutation p.Arg220Gln

Purpose Heterozygous peripherin mutation is associated with a wide range of typically adult-onset retinal phenotypes which can include asymptomatic maculopathy. There are few reports of biallelic peripherin mutations, only one of which detailed the ophthalmic phenotype. This report documents the retinal phenotype associated with homozygosity for a known peripherin mutation (c.659G>A; p.Arg220Gln), highlights its similar appearance to what was described in the one previous report, and shows how examination of family members can be useful in genetic diagnosis. Methods Retrospective case series. Results A 13-year-old Emirati boy was referred for low vision. The parents felt he was blind at birth but noted improvement with time. Retinal examination was significant for central macula horizontal ovoid discoloration as was documented for young adults with homozygous peripherin mutations in the one previous report. Electroretinography revealed cone-rod dysfunction. Both asymptomatic parents were examined and found to have central macular abnormalities. Sanger sequencing of peripherin based on clinical features uncovered the pathogenic variant c.659G>A; p.Arg22Gln (NM_000322.4) in homozygosity in the child and in heterozygosity in each parent. Exome sequencing in the child excluded pathologic variants in other retinal dystrophy genes. Conclusions The experience with this family highlights clinical features suggestive for biallelic peripherin mutations, documents cone-rod dysfunction as associated with homozygosity for the p.Arg220Gln peripherin mutation, and is an example of how examination of family members can help to guide genetic testing.