RP2 and RPGR mutations and clinical correlations in patients with X-linked retinitis pigmentosa

Am J Hum Genet. 2003 Nov;73(5):1131-46. doi: 10.1086/379379. Epub 2003 Oct 16.


We determined the mutation spectrum of the RP2 and RPGR genes in patients with X-linked retinitis pigmentosa (XLRP) and searched for correlations between categories of mutation and severity of disease. We screened 187 unrelated male patients for mutations, including 135 with a prior clinical diagnosis of XLRP, 11 with probable XLRP, 30 isolate cases suspected of having XLRP, and 11 with cone-rod degeneration. Mutation screening was performed by single-strand conformation analysis and by sequencing of all RP2 exons and RPGR exons 1-14, ORF15, and 15a. The refractive error, visual acuity, final dark-adapted threshold, visual field area, and 30-Hz cone electroretinogram (ERG) amplitude were measured in each patient. Among the 187 patients, we found 10 mutations in RP2, 2 of which are novel, and 80 mutations in RPGR, 41 of which are novel; 66% of the RPGR mutations were within ORF15. Among the 135 with a prior clinical diagnosis of XLRP, mutations in the RP2 and RPGR genes were found in 9 of 135 (6.7%) and 98 of 135 (72.6%), respectively, for a total of 79% of patients. Patients with RP2 mutations had, on average, lower visual acuity but similar visual field area, final dark-adapted threshold, and 30-Hz ERG amplitude compared with those with RPGR mutations. Among patients with RPGR mutations, those with ORF15 mutations had, on average, a significantly larger visual field area and a borderline larger ERG amplitude than did patients with RPGR mutations in exons 1-14. Among patients with ORF15 mutations, regression analyses showed that the final dark-adapted threshold became lower (i.e., closer to normal) and that the 30-Hz ERG amplitude increased as the length of the wild-type ORF15 amino acid sequence increased. Furthermore, as the length of the abnormal amino acid sequence following ORF15 frameshift mutations increased, the severity of disease increased.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Chromosomes, Human, X / genetics*
  • DNA Mutational Analysis
  • Dark Adaptation / physiology
  • Electroretinography
  • Exons / genetics
  • Eye Proteins / genetics*
  • GTP-Binding Proteins
  • Genetic Diseases, X-Linked / genetics*
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Male
  • Membrane Proteins
  • Middle Aged
  • Mutation / genetics*
  • Open Reading Frames / genetics
  • Phenotype
  • Retinitis Pigmentosa / genetics*
  • Retinitis Pigmentosa / physiopathology*
  • Visual Acuity / physiology
  • Visual Fields / physiology


  • Eye Proteins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • RP2 protein, human
  • RPGR protein, human
  • GTP-Binding Proteins

Associated data

  • OMIM/RP2
  • OMIM/RP24
  • OMIM/RP6