title: Positional cloning of the gene for X-linked retinitis pigmentosa 3: homology with the guanine-nucleotide-exchange factor RCC1.
abstract: The gene for retinitis pigmentosa 3 (RP3), the most frequent form of X-linked RP (XLRP), has been mapped previously to a chromosome interval of less than 1000 kbp between the DXS1110 marker and the OTC locus at Xp21.1-p11.4. Employing a novel technique, YAC Representation Hybridization (YRH)', we have recently identified a small XLRP associated microdeletion in this interval, as well as several putative exons including the 3' end of a gene that was truncated by the deletion. cDNA library screening and sequencing of a cosmid centromeric to the deletion has now enabled us to identify numerous additional exons and to detect several point mutations in patients with XLRP. The predicted gene product shows homology to RCC1, the guanine-nucleotide-exchange factor (GEF) of the Ras-like GTPase Ran. Our findings suggest that we have cloned the long-sought RP3 gene, and that it may encode the GEF of a retina-specific GTP-binding protein.
authors.affiliation: Department of Human Genetics, University Hospital Nijmegen, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Roepman
authors.forename: G
authors.initials: G
authors.lastname: van Duijnhoven
authors.forename: T
authors.initials: T
authors.lastname: Rosenberg
authors.forename: A J
authors.initials: AJ
authors.lastname: Pinckers
authors.forename: L M
authors.initials: LM
authors.lastname: Bleeker-Wagemakers
authors.forename: A A
authors.initials: AA
authors.lastname: Bergen
authors.forename: J
authors.initials: J
authors.lastname: Post
authors.forename: A
authors.initials: A
authors.lastname: Beck
authors.forename: R
authors.initials: R
authors.lastname: Reinhardt
authors.forename: H H
authors.initials: HH
authors.lastname: Ropers
authors.forename: F P
authors.initials: FP
authors.lastname: Cremers
authors.forename: W
authors.initials: W
authors.lastname: Berger
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D018797:Cell Cycle Proteins; D003001:Cloning, Molecular; D003360:Cosmids; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005136:Eye Proteins; D005796:Genes; D008040:Genetic Linkage; D020662:Guanine Nucleotide Exchange Factors; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D009928:Organ Specificity; D017354:Point Mutation / Q000235:genetics; D011110:Polymorphism, Genetic; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D012174:Retinitis Pigmentosa / Q000235:genetics*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D012689:Sequence Homology, Nucleic Acid; D014960:X Chromosome / Q000235:genetics; D020663:ras Guanine Nucleotide Exchange Factors
chemical_list: D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D005136:Eye Proteins; D020662:Guanine Nucleotide Exchange Factors; D009687:Nuclear Proteins; D011506:Proteins; C062521:RCC1 protein, human; D012333:RNA, Messenger; C099929:RPGR protein, human; D020663:ras Guanine Nucleotide Exchange Factors