Association of a novel mutation in the retinol dehydrogenase 12 (RDH12) gene with autosomal dominant retinitis pigmentosa

Arch Ophthalmol. 2008 Sep;126(9):1301-7. doi: 10.1001/archopht.126.9.1301.


Objective: To identify the gene causing retinitis pigmentosa (RP) in an autosomal dominant pedigree.

Methods: Family members with RP were studied with linkage analysis using single-nucleotide polymorphism and short tandem repeat polymorphic markers. Candidate genes in the linked region were evaluated with DNA sequencing.

Results: Nineteen family members had a mild form of RP. Multipoint linkage analysis of single-nucleotide polymorphism genotypes yielded a maximum nonparametric linkage score of 19.97 with markers located on chromosome 14q. LOD scores higher than 3.0 were obtained with 20 short tandem repeat polymorphic markers, and recombinants defined a 21.7-centimorgan locus on chromosome 14q. The retinol dehydrogenase 12 (RDH12) gene lies within this locus and was evaluated as a candidate gene. A frameshift mutation (776delG) was detected in all affected family members and was not detected in 158 control subjects.

Conclusions: Heterozygous mutations in RDH12 can cause autosomal dominant RP with a late onset and relatively mild severity. This phenotype is dramatically different from the other disease associated with mutation in this gene, autosomal recessive Leber congenital amaurosis.

Clinical relevance: The demonstration that mutations in a gene previously associated with recessive Leber congenital amaurosis can also cause dominant RP illustrates the wide phenotypic variability of retinal degeneration genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alcohol Oxidoreductases / genetics*
  • Child
  • Chromosome Mapping
  • Chromosomes, Human, Pair 14 / genetics
  • Electroretinography
  • Female
  • Frameshift Mutation*
  • Genes, Dominant*
  • Genotype
  • Humans
  • Lod Score
  • Male
  • Pedigree
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide
  • Retinitis Pigmentosa / diagnosis
  • Retinitis Pigmentosa / genetics*
  • Visual Field Tests


  • Alcohol Oxidoreductases
  • RDH12 protein, human