title: A human homolog of yeast pre-mRNA splicing gene, PRP31, underlies autosomal dominant retinitis pigmentosa on chromosome 19q13.4 (RP11).
abstract: We report mutations in a gene (PRPF31) homologous to Saccharomyces cerevisiae pre-mRNA splicing gene PRP31 in families with autosomal dominant retinitis pigmentosa linked to chromosome 19q13.4 (RP11; MIM 600138). A positional cloning approach supported by bioinformatics identified PRPF31 comprising 14 exons and encoding a protein of 499 amino acids. The level of sequence identity to the yeast PRP31 gene indicates that PRPF31 is also likely to be involved in pre-mRNA splicing. Mutations that include missense substitutions, deletions, and insertions have been identified in four RP11-linked families and three sporadic RP cases. The identification of mutations in a pre-mRNA splicing gene implicates defects in the splicing process as a novel mechanism of photoreceptor degeneration.
authors.affiliation: Department of Molecular Genetics, Institute of Ophthalmology, University College London, ECIV 9EL, London, United Kingdom.
authors.forename: E N
authors.initials: EN
authors.lastname: Vithana
authors.forename: L
authors.initials: L
authors.lastname: Abu-Safieh
authors.forename: M J
authors.initials: MJ
authors.lastname: Allen
authors.forename: A
authors.initials: A
authors.lastname: Carey
authors.forename: M
authors.initials: M
authors.lastname: Papaioannou
authors.forename: C
authors.initials: C
authors.lastname: Chakarova
authors.forename: M
authors.initials: M
authors.lastname: Al-Maghtheh
authors.forename: N D
authors.initials: ND
authors.lastname: Ebenezer
authors.forename: C
authors.initials: C
authors.lastname: Willis
authors.forename: A T
authors.initials: AT
authors.lastname: Moore
authors.forename: A C
authors.initials: AC
authors.lastname: Bird
authors.forename: D M
authors.initials: DM
authors.lastname: Hunt
authors.forename: S S
authors.initials: SS
authors.lastname: Bhattacharya
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D002888:Chromosomes, Human, Pair 19; D003001:Cloning, Molecular; D019295:Computational Biology; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D008040:Genetic Linkage; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D020161:Physical Chromosome Mapping; D012326:RNA Splicing / Q000235:genetics*; D012174:Retinitis Pigmentosa / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D017381:Spliceosomes
chemical_list: D005656:Fungal Proteins; C491451:PRP31 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins