Spectrum of mutations in the RPGR gene that are identified in 20% of families with X-linked retinitis pigmentosa

Am J Hum Genet. 1997 Dec;61(6):1287-92. doi: 10.1086/301646.


The RPGR (retinitis pigmentosa GTPase regulator) gene for RP3, the most frequent genetic subtype of X-linked retinitis pigmentosa (XLRP), has been shown to be mutated in 10%-15% of European XLRP patients. We have examined the RPGR gene for mutations in a cohort of 80 affected males from apparently unrelated XLRP families, by direct sequencing of the PCR-amplified products from the genomic DNA. Fifteen different putative disease-causing mutations were identified in 17 of the 80 families; these include four nonsense mutations, one missense mutation, six microdeletions, and four intronic-sequence substitutions resulting in splice defects. Most of the mutations were detected in the conserved N-terminal region of the RPGR protein, containing tandem repeats homologous to those present in the RCC-1 protein (a guanine nucleotide-exchange factor for Ran-GTPase). Our results indicate that mutations either in as yet uncharacterized sequences of the RPGR gene or in another gene located in its vicinity may be a more frequent cause of XLRP. The reported studies will be beneficial in establishing genotype-phenotype correlations and should lead to further investigations seeking to understand the mechanism of disease pathogenesis.

Publication types

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

MeSH terms

  • Carrier Proteins / genetics*
  • Cohort Studies
  • DNA Mutational Analysis
  • Exons / genetics
  • Eye Proteins*
  • Humans
  • Male
  • Point Mutation
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • RNA Splicing
  • Retinitis Pigmentosa / genetics*
  • Sequence Deletion
  • X Chromosome / genetics*


  • Carrier Proteins
  • Eye Proteins
  • RPGR protein, human