title: Molecular analysis of ABCA4 and CRB1 genes in a Spanish family segregating both Stargardt disease and autosomal recessive retinitis pigmentosa.
abstract: OBJECTIVE
  Stargardt disease (STGD), characterized by central visual impairment, is the most common juvenile macular dystrophy. All recessively inherited cases are thought to be due to mutations in the ABCA4 gene. Early-onset autosomal recessive retinitis pigmentosa (arRP) is a severe retinal degeneration that presents before the patient is ten years old. It has been associated with mutations in different genes, including CRB1. The aim of this study was to determine the genetic causes for two different retinal dystrophies, STGD and early-onset arRP, both segregating in one Spanish family.
  
  
  METHODS
  Mutational analyses were performed using the ABCR400 and Leber congenital amaurosis (LCA) genotyping microarrays. Additional scanning for mutations was conducted by denaturing high performance liquid chromatography (dHPLC); results were confirmed by direct sequencing.
  
  
  RESULTS
  A patient, who exhibited a STGD phenotype, was found to be homozygous for the p.Asn1805Asp (c.5413A>G) mutation in ABCA4. However, his affected sister, who had the arRP phenotype, was found to be heterozygous for this allele; no other sequence change could be found in ABCA4. Analysis using the LCA chip revealed the p.Cys948Tyr mutation in CRB1 in heterozygous state. A second mutation (p.Trp822ter) was found in the CRB1 gene in the affected female by denaturing high performance liquid chromatography (dHPLC) and direct sequencing.
  
  
  CONCLUSIONS
  Two distinct retinal dystrophies with mutations affecting two different genes cosegregated in this family. The presence of two different phenotypes associated with mutations in two distinct genes in one single family must be considered especially when dealing with retinal dystrophies which bear high carrier frequencies in general population.
authors.affiliation: Genetics Department, Fundacion Jimenez Diaz-CIBERER, Madrid, Spain. rriveiro@fjd.es
authors.forename: Rosa
authors.initials: R
authors.lastname: Riveiro-Alvarez
authors.forename: Elena
authors.initials: E
authors.lastname: Vallespin
authors.forename: Robert
authors.initials: R
authors.lastname: Wilke
authors.forename: Blanca
authors.initials: B
authors.lastname: Garcia-Sandoval
authors.forename: Diego
authors.initials: D
authors.lastname: Cantalapiedra
authors.forename: Jana
authors.initials: J
authors.lastname: Aguirre-Lamban
authors.forename: Almudena
authors.initials: A
authors.lastname: Avila-Fernandez
authors.forename: Ascension
authors.initials: A
authors.lastname: Gimenez
authors.forename: Maria-Jose
authors.initials: MJ
authors.lastname: Trujillo-Tiebas
authors.forename: Carmen
authors.initials: C
authors.lastname: Ayuso
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D020090:Chromosome Segregation; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D008268:Macular Degeneration / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D012174:Retinitis Pigmentosa / Q000453:epidemiology / Q000235:genetics*; D013030:Spain / Q000453:epidemiology; D044465:White People / Q000235:genetics*
chemical_list: C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters; C448939:CRB1 protein, human; D005136:Eye Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins