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RPGR ORF15 genotype and clinical variability of retinal degeneration in an Australian population
  1. J B Ruddle1,2,
  2. N D Ebenezer3,
  3. L S Kearns1,
  4. L E Mulhall2,
  5. D A Mackey1,2,
  6. A J Hardcastle3
  1. 1
    Centre for Eye Research Australia, East Melbourne, Australia
  2. 2
    Ocular Diagnostic Clinic, Royal Victorian Eye and Ear Hospital, East Melbourne, Australia
  3. 3
    UCL Institute of Ophthalmology, London, UK
  1. Correspondence to Dr J Ruddle, Centre for Eye Research Australia, 32 Gisborne St, East Melbourne 3002, Australia; jbruddle{at}gmail.com

Abstract

Background: Mutations in the retinitis pigmentosa GTPase regulator gene (RPGR) are estimated to cause up to 20% of all Caucasian retinitis pigmentosa and up to 75% of cases of X-Linked RP (XLRP). Exon open reading frame 15 (ORF15) is a purine-rich mutation hotspot. Mutations in RPGR ORF15 have also been documented to cause X linked cone–rod dystrophy (XLCORD) and atrophic macular degeneration at an unknown frequency.

Methods: From a hospital clinic population, probands with probable XLRP and XLCORD were screened for RPGR ORF15 mutations and fully phenotyped.

Results: Four different RPGR ORF15 mutations were found in four probands. All mutations in the ORF15 exon resulted in premature truncation of the RPGR protein. Three were nonsense mutations: c.507G>T (p.E169stop), c.867G>T (p.G289stop), c.897G>T (p.E299stop) and the fourth a single nucleotide insertion c.1558–1559insA (p.S522fs 525stop). One family exhibited typical XLRP, two XLCORD and one a combination of the phenotypes.

Conclusion: RPGR ORF15 mutations produce intrafamilial and interfamilial clinical variability with varying degrees of cone degeneration. In an Australian clinic population RPGR ORF15 mutations cause XLCORD in addition to XLRP.

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Footnotes

  • Funding This research was supported by grant 065454/Z/01/Z from the Wellcome Trust.

  • Competing interests None.

  • Provenance and Peer review Not commissioned; externally peer reviewed.

  • Ethics approval Ethics approval was provided by the Royal Victorian Eye and Ear Hospital, Melbourne.

  • Patient consent Obtained.

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