title: Prevalence of Rhodopsin mutations in autosomal dominant Retinitis Pigmentosa in Spain: clinical and analytical review in 200 families.
abstract: OBJECTIVE
  We aimed to determine the prevalence of mutations in the RHO gene in Spanish families with autosomal dominant Retinitis Pigmentosa (adRP), to assess genotype-phenotype correlations and to establish an accurate diagnostic algorithm after 23 years of data collection.
  
  
  METHODS
  Two hundred patients were analysed through a combination of denaturing gradient gel electrophoresis, single-strand conformation polymorphism, genotyping microarray and Sanger sequencing of the RHO gene.
  
  
  RESULTS
  Overall, 42 of 200 Spanish adRP families were mutated for RHO (21.0%). Twenty-seven different RHO mutations were detected; seven of them were novel. A genotype-phenotype correlation was established with clinical data from 107 patients. The most prevalent p.Pro347Leu mutation, responsible for 4.5% (9/200) of all mutated adRP families, was associated with a phenotype of early onset and severe course diffuse RP.
  
  
  CONCLUSIONS
  This retrospective study provides a wide spectrum of mutations in the RHO gene in Spanish patients with adRP. Also, the prevalence of mutations is similar to that reported in European population. Genotyping microarray followed by RHO sequencing is proposed as a first step in molecular diagnosis of adRP Spanish families. An increasing understanding of causal RHO alleles in adRP facilitates disease diagnosis and prognosis, especially for the prevalent p.Pro347Leu mutation.
authors.affiliation: Department of Genetics, Health Research Institute Fundacion Jimenez Diaz, University Hospital (IIS-FJD, UAM), Madrid, Spain; Centre for Biomedical Network Research on Rare Diseases CIBERER, ISCIII, Madrid, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Fernandez-San Jose
authors.forename: Fiona
authors.initials: F
authors.lastname: Blanco-Kelly
authors.forename: Marta
authors.initials: M
authors.lastname: Corton
authors.forename: Maria-Jose
authors.initials: MJ
authors.lastname: Trujillo-Tiebas
authors.forename: Ascension
authors.initials: A
authors.lastname: Gimenez
authors.forename: Almudena
authors.initials: A
authors.lastname: Avila-Fernandez
authors.forename: Blanca
authors.initials: B
authors.lastname: Garcia-Sandoval
authors.forename: Maria-Isabel
authors.initials: MI
authors.lastname: Lopez-Molina
authors.forename: Inma
authors.initials: I
authors.lastname: Hernan
authors.forename: Miguel
authors.initials: M
authors.lastname: Carballo
authors.forename: Rosa
authors.initials: R
authors.lastname: Riveiro-Alvarez
authors.forename: Carmen
authors.initials: C
authors.lastname: Ayuso
mesh_terms: D000328:Adult; D004252:DNA Mutational Analysis; D005260:Female; D056726:Genetic Association Studies; D060005:Genotyping Techniques; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D018807:Polymorphism, Single-Stranded Conformational; D015995:Prevalence; D012174:Retinitis Pigmentosa / Q000175:diagnosis / Q000235:genetics*; D012189:Retrospective Studies; D012243:Rhodopsin / Q000235:genetics*; D013030:Spain
chemical_list: D012243:Rhodopsin
keywords: RHO; Retinitis Pigmentosa; Spanish families; autosomal dominant; diagnostic algorithm; genotype-phenotype correlation