CERKL mutations and associated phenotypes in seven Spanish families with autosomal recessive retinitis pigmentosa

Invest Ophthalmol Vis Sci. 2008 Jun;49(6):2709-13. doi: 10.1167/iovs.07-0865.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Electroretinography
  • Genes, Recessive*
  • Genotype
  • Humans
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Phenotype
  • Phosphotransferases (Alcohol Group Acceptor) / genetics*
  • Point Mutation*
  • Polymerase Chain Reaction
  • Retinitis Pigmentosa / diagnosis
  • Retinitis Pigmentosa / genetics*
  • Spain
  • Visual Acuity
  • Visual Fields

Substances

  • Phosphotransferases (Alcohol Group Acceptor)
  • ceramide kinase