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RPGR ORF15 Genotype and Clinical Variability of Retinal Degeneration in an Australian Population
  1. Jonathan B Ruddle (jbruddle{at},
  2. Neil D Ebenezer,
  3. Lisa S Kearns (lkearns{at},
  4. Lindsay E Mulhall (lindsay.mulhall{at},
  5. David A Mackey (d.mackey{at},
  6. Alison J Hardcastle (a.hardcastle{at}
  1. Centre for Eye Research, Australia
  2. UCL Institute of Ophthalmology, United Kingdom
  3. Centre for Eye Research, Australia
  4. Royal Victorian Eye and Ear Hospital, Australia
  5. Centre for Eye Research, Australia
  6. UCL Institute of Ophthalmology, United Kingdom


    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 4 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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