title: Identification and characterization of a novel RPGR isoform in human retina.
abstract: Retinitis pigmentosa (RP) constitutes a major cause of blindness and the Retinitis Pigmentosa GTPase Regulator (RPGR) gene accounts for up to 80% of all X-linked RP cases. A novel isoform of RPGR, expressed in the human retina, was identified and characterized. It truncates the Regulator of Chromosome Condensation 1 (RCC1) homologous protein domain (RCC1h) of RPGR and mediates the formation of isoform-specific complexes with the RPGR-interacting protein 1 (RPGRIP1). Immunohistochemistry localized the novel RPGR isoform predominantly to inner segments of cone photoreceptors, where it colocalizes with RPGRIP1 in the human retina. In a patient with a mild RP phenotype, we identified a nucleotide substitution in a splicing regulator, which leads to 3.5 times higher levels of the transcripts coding for the novel RPGR isoform. The nucleotide substitution affects regulated alternative splicing of the novel RPGR isoform and suggests a tight adjustment of splicing as a prerequisite for proper function of photoreceptors.
authors.affiliation: Division of Medical Molecular Genetics and Gene Diagnostics, Institute of Medical Genetics, University of Zurich, Zurich, Switzerland. neidhardt@medgen.uzh.ch
authors.forename: John
authors.initials: J
authors.lastname: Neidhardt
authors.forename: Esther
authors.initials: E
authors.lastname: Glaus
authors.forename: Daniel
authors.initials: D
authors.lastname: Barthelmes
authors.forename: Christina
authors.initials: C
authors.lastname: Zeitz
authors.forename: Johannes
authors.initials: J
authors.lastname: Fleischhauer
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Berger
mesh_terms: D001483:Base Sequence; D019295:Computational Biology; D003598:Cytoskeletal Proteins; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005136:Eye Proteins / Q000737:chemistry / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D011485:Protein Binding; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011506:Proteins / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D012174:Retinitis Pigmentosa / Q000235:genetics / Q000473:pathology; D040681:Structural Homology, Protein
chemical_list: D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D020033:Protein Isoforms; D011506:Proteins; C099929:RPGR protein, human; C415903:RPGRIP1 protein, human