Spectrum of mutations in the RPGR gene that are identified in 20% of families with X-linked retinitis pigmentosa.
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.
Buraczynska
M
M
Department of Ophthalmology, W.K. Kellogg Eye Center, University of Michigan, Ann Arbor 48105, USA.
Wu
W
W
Fujita
R
R
Buraczynska
K
K
Phelps
E
E
Andréasson
S
S
Bennett
J
J
Birch
D G
DG
Fishman
G A
GA
Hoffman
D R
DR
Inana
G
G
Jacobson
S G
SG
Musarella
M A
MA
Sieving
P A
PA
Swaroop
A
A
D002352:Carrier Proteins / Q000235:genetics*; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005136:Eye Proteins; D006801:Humans; D008297:Male; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012326:RNA Splicing; D012174:Retinitis Pigmentosa / Q000235:genetics*; D017384:Sequence Deletion; D014960:X Chromosome / Q000235:genetics*
D002352:Carrier Proteins; D005136:Eye Proteins; C099929:RPGR protein, human