RP1 and autosomal dominant rod-cone dystrophy: novel mutations, a review of published variants, and genotype-phenotype correlation

Hum Mutat. 2012 Jan;33(1):73-80. doi: 10.1002/humu.21640. Epub 2011 Dec 1.

Abstract

Rod-cone dystrophies (retinitis pigmentosa [RP]) are a clinically and genetically heterogeneous group of inherited retinal disorders characterized by photoreceptor degeneration. RP1 is a major gene underlying autosomal dominant (ad) RP, though prevalence figures vary depending on the origin of the cases from 0-10% of all adRP. Some mutations in RP1 also lead to autosomal recessive (ar) RP. Herein, we review all previously reported and several novel RP1 mutations in relation to the associated phenotype in RP1 patients from a French adRP cohort. Prevalence studies from this cohort show that 5.3% of the cases have RP1 mutations. This is in accordance with other studies reported from United Kingdom and United States. The majority of mutations represent truncating mutations that are located in a hot spot region of the gene. Similarly, we identified in total four novel deletions and nonsense mutations, of which two may represent recurrent mutations in this population. In addition, a novel missense mutation of uncertain pathogenicity was identified. Including our findings to date, 47 RP1 mutations are known to cause adRP. Variable penetrance of the disease was observed in our and other cohorts. Most patients with RP1 mutations show classical signs of RP with relatively preserved central vision and visual field.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Codon, Nonsense
  • Cohort Studies
  • DNA Mutational Analysis
  • Eye Proteins / genetics*
  • Female
  • France
  • Genes, Dominant
  • Genetic Association Studies*
  • Genetic Variation
  • Genotype
  • Haploinsufficiency
  • Haplotypes
  • Humans
  • Male
  • Microtubule-Associated Proteins
  • Middle Aged
  • Mutation, Missense
  • Pedigree
  • Phenotype
  • Prevalence
  • Retinal Rod Photoreceptor Cells / metabolism*
  • Retinal Rod Photoreceptor Cells / pathology
  • Retinitis Pigmentosa / diagnosis
  • Retinitis Pigmentosa / epidemiology
  • Retinitis Pigmentosa / genetics*
  • Sequence Deletion

Substances

  • Codon, Nonsense
  • Eye Proteins
  • Microtubule-Associated Proteins
  • RP1 protein, human