CERKLMutations and Associated Phenotypes in Seven Spanish Families with Autosomal Recessive Retinitis Pigmentosa

PURPOSE: Retinitis pigmentosa (RP) is a genetically heterogeneous group of inherited retinopathies. Up to now, 39 genes and loci have been implicated in nonsyndromic RP, yet the genetic bases of >50% of the cases, particularly of the recessive forms, remain unknown. A novel gene (CERKL) has been described as associated with RP26. It encodes a ceramide kinase that is assumed to be involved in sphingolipid-mediated apoptosis in the retina. This is a report of the phenotypes and genotypes of persons carrying disease-causing mutations in CERKL. METHODS: Two hundred ten unrelated Spanish families with nonsyndromic autosomal recessive RP were analyzed for sequence variations. Seven of these families presented a mutation in CERKL. Nine affected persons of these families were clinically investigated, including visual field, electrophysiology, and fundus examination. RESULTS: The mutation p.Arg257ter was identified in the homozygous state in all seven affected families. The patients with this variation in CERKL presented a common phenotype with characteristic macular and peripheral lesions. CONCLUSIONS: This study presents the first genotype-phenotype correlation for persons carrying p.Arg257ter mutation and provides clues for a characteristic phenotype of these mutations among persons with autosomal recessive cases.