title: Spectrum of mutations in the RPGR gene that are identified in 20% of families with X-linked retinitis pigmentosa.
abstract: 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.
authors.affiliation: Department of Ophthalmology, W.K. Kellogg Eye Center, University of Michigan, Ann Arbor 48105, USA.
authors.forename: M
authors.initials: M
authors.lastname: Buraczynska
authors.forename: W
authors.initials: W
authors.lastname: Wu
authors.forename: R
authors.initials: R
authors.lastname: Fujita
authors.forename: K
authors.initials: K
authors.lastname: Buraczynska
authors.forename: E
authors.initials: E
authors.lastname: Phelps
authors.forename: S
authors.initials: S
authors.lastname: Andréasson
authors.forename: J
authors.initials: J
authors.lastname: Bennett
authors.forename: D G
authors.initials: DG
authors.lastname: Birch
authors.forename: G A
authors.initials: GA
authors.lastname: Fishman
authors.forename: D R
authors.initials: DR
authors.lastname: Hoffman
authors.forename: G
authors.initials: G
authors.lastname: Inana
authors.forename: S G
authors.initials: SG
authors.lastname: Jacobson
authors.forename: M A
authors.initials: MA
authors.lastname: Musarella
authors.forename: P A
authors.initials: PA
authors.lastname: Sieving
authors.forename: A
authors.initials: A
authors.lastname: Swaroop
mesh_terms: 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*
chemical_list: D002352:Carrier Proteins; D005136:Eye Proteins; C099929:RPGR protein, human