title: Clinical studies of X-linked retinitis pigmentosa in three Swedish families with newly identified mutations in the RP2 and RPGR-ORF15 genes.
abstract: OBJECTIVE
  To describe new disease-causing RP2 and RPGR-ORF15 mutations and their corresponding clinical phenotypes in Swedish families with X-linked retinitis pigmentosa (XLRP) and to establish genotype-phenotype correlations by studying the clinical spectrum of disease in families with a known molecular defect.
  
  
  METHODS
  Seventeen unrelated families with RP and an apparent X-linked pattern of disease inheritance were identified from the Swedish RP registry and screened for mutations in the RP2 and RPGR (for the RP3 disease) genes. These families had been previously screened for the RPGR exons 1-19, and disease-causing mutations were identified in four of them. In the remaining 13 families, we sequenced the RP2 gene and the newly discovered RPGR-ORF exon. Detailed clinical evaluations were then obtained from individuals in the three families with identified mutations.
  
  
  RESULTS
  Mutations in RP2 and RPGR-ORF15 were identified in three of the 13 families. Clinical evaluations of affected males and carrier females demonstrated varying degrees of retinal dysfunction and visual handicap, with early onset and severe disease in the families with mutations in the ORF15 exon of the RPGR gene.
  
  
  CONCLUSIONS
  A total of seven mutations in the RP2 and RPGR genes have been discovered so far in Swedish XLRP families. All affected individuals express a severe form of retinal degeneration with visual handicap early in life, although the degree of retinal dysfunction varies both in hemizygous male patients and in heterozygous carrier females. Retinal disease phenotypes in patients with mutations in the RPGR-ORF15 were more severe than in patients with mutations in RP2 or other regions of the RPGR.
authors.affiliation: Department of Ophthalmology, University Hospital of Lund, Lund, Sweden. sten.andreasson@oft.lu.se
authors.forename: Sten
authors.initials: S
authors.lastname: Andréasson
authors.forename: Debra K
authors.initials: DK
authors.lastname: Breuer
authors.forename: Louise
authors.initials: L
authors.lastname: Eksandh
authors.forename: Vesna
authors.initials: V
authors.lastname: Ponjavic
authors.forename: Christina
authors.initials: C
authors.lastname: Frennesson
authors.forename: Suja
authors.initials: S
authors.lastname: Hiriyanna
authors.forename: Elena
authors.initials: E
authors.lastname: Filippova
authors.forename: Beverly M
authors.initials: BM
authors.lastname: Yashar
authors.forename: Anand
authors.initials: A
authors.lastname: Swaroop
mesh_terms: D000328:Adult; D000368:Aged; D002352:Carrier Proteins / Q000235:genetics*; D041321:Chromosomes, Human, X / Q000235:genetics*; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005091:Exons / Q000235:genetics; D005136:Eye Proteins; D005260:Female; D019204:GTP-Binding Proteins; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D016366:Open Reading Frames; D010375:Pedigree; D011506:Proteins / Q000235:genetics*; D012174:Retinitis Pigmentosa / Q000235:genetics*; D013548:Sweden; D014792:Visual Acuity; D014794:Visual Fields
chemical_list: D002352:Carrier Proteins; D005136:Eye Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D011506:Proteins; C072178:RP2 protein, human; C099929:RPGR protein, human; D019204:GTP-Binding Proteins