title: Three novel and the common Arg677Ter RP1 protein truncating mutations causing autosomal dominant retinitis pigmentosa in a Spanish population.
abstract: BACKGROUND
  Retinitis pigmentosa (RP), a clinically and genetically heterogeneous group of retinal degeneration disorders affecting the photoreceptor cells, is one of the leading causes of genetic blindness. Mutations in the photoreceptor-specific gene RP1 account for 3-10% of cases of autosomal dominant RP (adRP). Most of these mutations are clustered in a 500 bp region of exon 4 of RP1.
  
  
  METHODS
  Denaturing gradient gel electrophoresis (DGGE) analysis and direct genomic sequencing were used to evaluate the 5' coding region of exon 4 of the RP1 gene for mutations in 150 unrelated index adRP patients. Ophthalmic and electrophysiological examination of RP patients and relatives according to pre-existing protocols were carried out.
  
  
  RESULTS
  Three novel disease-causing mutations in RP1 were detected: Q686X, K705fsX712 and K722fsX737, predicting truncated proteins. One novel missense mutation, Thr752Met, was detected in one family but the mutation does not co-segregate in the family, thereby excluding this amino acid variation in the protein as a cause of the disease. We found the Arg677Ter mutation, previously reported in other populations, in two independent families, confirming that this mutation is also present in a Spanish population.
  
  
  CONCLUSIONS
  Most of the mutations reported in the RP1 gene associated with adRP are expected to encode mutant truncated proteins that are approximately one third or half of the size of wild type protein. Patients with mutations in RP1 showed mild RP with variability in phenotype severity. We also observed several cases of non-penetrant mutations.
authors.affiliation: Servicio de Laboratorio, Hospital de Terrassa, Ctra, Torrebonica s/n 08227 Terrassa, Barcelona, España. lab-biomolecular@csdt.es
authors.forename: María José
authors.initials: MJ
authors.lastname: Gamundi
authors.forename: Imma
authors.initials: I
authors.lastname: Hernan
authors.forename: María
authors.initials: M
authors.lastname: Martínez-Gimeno
authors.forename: Miquel
authors.initials: M
authors.lastname: Maseras
authors.forename: Blanca
authors.initials: B
authors.lastname: García-Sandoval
authors.forename: Carmen
authors.initials: C
authors.lastname: Ayuso
authors.forename: Guillermo
authors.initials: G
authors.lastname: Antiñolo
authors.forename: Montserrat
authors.initials: M
authors.lastname: Baiget
authors.forename: Miguel
authors.initials: M
authors.lastname: Carballo
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001120:Arginine / Q000235:genetics; D004252:DNA Mutational Analysis; D005091:Exons; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008869:Microtubule-Associated Proteins; D020125:Mutation, Missense; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D012174:Retinitis Pigmentosa / Q000175:diagnosis / Q000235:genetics*; D017384:Sequence Deletion; D013030:Spain
chemical_list: D005136:Eye Proteins; D008869:Microtubule-Associated Proteins; C120042:RP1 protein, human; D001120:Arginine