title: Mutations in a gene encoding a new oxygen-regulated photoreceptor protein cause dominant retinitis pigmentosa.
abstract: The autosomal dominant retinitis pigmentosa (RP) locus, designated RP1, has been mapped through linkage studies to a 4-cM interval at 8q11-13. Here we describe a new photoreceptor-specific gene that maps in this interval and whose expression is modulated by retinal oxygen levels in vivo. This gene consists of at least 4 exons that encode a predicted protein of 2,156 amino acids. A nonsense mutation at codon 677 of this gene is present in approximately 3% of cases of dominant RP in North America. We also detected two deletion mutations that cause frameshifts and introduce premature termination codons in three other families with dominant RP. Our data suggest that mutations in this gene cause dominant RP, and that the encoded protein has an important but unknown role in photoreceptor biology.
authors.affiliation: F.M. Kirby Center for Molecular Ophthalmology, University of Pennsylvania, Scheie Eye Institute, Philadelphia, USA. epierce@mail.med.upenn.edu
authors.forename: E A
authors.initials: EA
authors.lastname: Pierce
authors.forename: T
authors.initials: T
authors.lastname: Quinn
authors.forename: T
authors.initials: T
authors.lastname: Meehan
authors.forename: T L
authors.initials: TL
authors.lastname: McGee
authors.forename: E L
authors.initials: EL
authors.lastname: Berson
authors.forename: T P
authors.initials: TP
authors.lastname: Dryja
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D004247:DNA / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009154:Mutation; D010100:Oxygen / Q000378:metabolism; D010375:Pedigree; D010641:Phenotype; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism*; D012174:Retinitis Pigmentosa / Q000235:genetics*
chemical_list: D017931:DNA Primers; D005136:Eye Proteins; D004247:DNA; D010100:Oxygen