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 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.