title: Mutations in the pre-mRNA splicing-factor genes PRPF3, PRPF8, and PRPF31 in Spanish families with autosomal dominant retinitis pigmentosa.
abstract: OBJECTIVE
  Mutations in the systemically expressed pre-mRNA splicing-factor genes PRPF3, PRPF8, and PRPF31 have recently been associated with autosomal dominant retinitis pigmentosa (adRP). This study was intended to identify mutations in PRPF3, PRPF8, and PRPF31 in 150 Spanish families affected by adRP, to measure the contribution of mutations in these genes to adRP in that population, and to correlate RP phenotype expression with mutations in pre-mRNA splicing-factor genes.
  
  
  METHODS
  Denaturing gradient gel electrophoresis (DGGE) and direct genomic sequencing were used to evaluate the complete coding region and flanking intronic sequences of the PRPF31 gene, exon 42 of PRPF8, and exon 11 of PRPF3 for mutations in 150 unrelated index patients with adRP. Ophthalmic and electrophysiological examination of patients with RP and their relatives was performed according to preexisting protocols.
  
  
  RESULTS
  Three nonsense mutations caused by insertion and deletion sequences and two missense mutations (Arg2310Gly) and within the stop codon of the PRPF8 gene (TGA-->TTG), were detected in five unrelated heterozygous patients. Three patients were heterozygous carriers of different nonsense mutations in exon 8 of the PRPF31, gene and one Thr494Met mutation was found in exon 11 of the PRPF3 gene. Cosegregation of the mutation in PRPF8 and PRPF3 with adRP was observed. However, two nonsense mutations in PRPF31 causing adRP detected in two families showed asymptomatic carriers.
  
  
  CONCLUSIONS
  Nine mutations, six of which are novel, in the pre-mRNA splicing-factor genes PRPF3, PRPF8, and PRPF31, causing adRP have been identified in the Spanish population. Their contribution to adRP is approximately 5% after correction in relation to mutations found in other genes causing adRP. The patients carrying a mutation in the pre-mRNA splicing-factor PRPF8 gene showed a type 1 diffuse RP. The existence of asymptomatic carriers of the nonsense mutation in the PRPF31 gene suggests incomplete penetrance for these mutations in the families.
authors.affiliation: Laboratory of Biology and Molecular Genetics, Laboratory of Service, Consorci Sanitari de Terrassa, Hospital de Terrassa, Terrassa, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Martínez-Gimeno
authors.forename: María José
authors.initials: MJ
authors.lastname: Gamundi
authors.forename: Imma
authors.initials: I
authors.lastname: Hernan
authors.forename: Miquel
authors.initials: M
authors.lastname: Maseras
authors.forename: Elena
authors.initials: E
authors.lastname: Millá
authors.forename: Carmen
authors.initials: C
authors.lastname: Ayuso
authors.forename: Blanca
authors.initials: B
authors.lastname: García-Sandoval
authors.forename: Magdalena
authors.initials: M
authors.lastname: Beneyto
authors.forename: Concha
authors.initials: C
authors.lastname: Vilela
authors.forename: Montserrat
authors.initials: M
authors.lastname: Baiget
authors.forename: Guillermo
authors.initials: G
authors.lastname: Antiñolo
authors.forename: Miguel
authors.initials: M
authors.lastname: Carballo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D002352:Carrier Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D004585:Electrooculography; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012322:RNA Precursors / Q000235:genetics*; D012326:RNA Splicing / Q000235:genetics*; D016601:RNA-Binding Proteins; D012174:Retinitis Pigmentosa / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D017414:Ribonucleoprotein, U4-U6 Small Nuclear / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013030:Spain / Q000453:epidemiology
chemical_list: D002352:Carrier Proteins; D005136:Eye Proteins; D009687:Nuclear Proteins; C108507:PRPF3 protein, human; C454222:PRPF31 protein, human; C115374:PRPF8 protein, human; D012322:RNA Precursors; D016601:RNA-Binding Proteins; D017414:Ribonucleoprotein, U4-U6 Small Nuclear