RPGR ORF15 genotype and clinical variability of retinal degeneration in an Australian population.
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.


CONCLUSIONS
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.
Ruddle
J B
JB
Centre for Eye Research Australia, 32 Gisborne St, East Melbourne 3002, Australia. jbruddle@gmail.com
Ebenezer
N D
ND
Kearns
L S
LS
Mulhall
L E
LE
Mackey
D A
DA
Hardcastle
A J
AJ
D000293:Adolescent; D000328:Adult; D018389:Codon, Nonsense / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics*; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D012162:Retinal Degeneration / Q000235:genetics*; D014739:Victoria; D055815:Young Adult
D018389:Codon, Nonsense; D005136:Eye Proteins; C099929:RPGR protein, human