CERKL related autosomal recessive retinitis pigmentosa - A report on four affected members from a single family

This case report describes the phenotypes associated with ceramide kinase like protein ( CERKL ) retinitis pigmentosa (RP) in a family with four affected members. We performed a cross sectional study of four members from a single family with RP. The retinal features, electrophysiology findings, and genetic results are discussed. Next generation sequencing based genetic testing was performed in two of the four affected family members. The affected individuals consisted of a 42 year old female proband (II.4), her 39 year old sister (II.6), and her two nephews, aged 10 and 12 years (III.2 and III.3, respectively). The genetic testing of III.2 and III.3 revealed the presence of a pathogenic homozygous frameshift nonsense variant (c. 1045_1046delAT, p.Met349Valfs*19) in exon 7 of the CERKL gene. All four family members had central vision problems since childhood. The best corrected visual acuity of the young patients, III.2 and III.3, was 20/30 and 20/80, respectively. The older patients (II.4 and II.6) were able to perceive only hand movements at the time of examination. The common retinal features found in III.2 and III.3 at presentation were minimal optic disc pallor, arteriolar attenuation, early loss of macular photoreceptors, central scotomas, and near extinguished responses in full field electroretinogram (ERG). There were no pigmentary or chorioretinal atrophic changes in the retina noted in individuals III.2 and III.3. The common retinal features in the proband (II.4) and her sister (II.6) in their 5th and 4th decades were prominent vascular attenuation, optic disc pallor, total macular atrophy, peripheral bony spicule pigmentation/scalloped chorioretinal atrophic patches, and a nondetectable ERG. In conclusion, the study of this family highlights the possibility of a severe phenotype in autosomal recessive CERKL related RP due to the nonsense variant c. 1045_1046delAT, p.Met349Valfs*19, as observed in our two genetically confirmed patients. Identifying the retinal phenotype and specific pathogenic variant is essential for accurate genetic counselling, personalized visual rehabilitation, and potential targeted therapies.