title: Mutations in CRB1 are a relatively common cause of autosomal recessive early-onset retinal degeneration in the Israeli and Palestinian populations.
abstract: OBJECTIVE
  We evaluated the role of Crumbs homolog 1 (CRB1) in autosomal recessive (AR) retinal diseases in the Israeli and Palestinian populations using homozygosity mapping.
  
  
  METHODS
  Clinical analysis included family history, ocular examination, full-field electroretinography (ERG), and funduscopy. Molecular analysis included homozygosity mapping using whole genome single nucleotide polymorphism (SNP) arrays and mutation analysis of CRB1.
  
  
  RESULTS
  We recruited over 400 families with AR nonsyndromic retinal degenerations, including retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA). SNP array analysis was performed on 175 index cases, eight of whom carried a homozygous region on chromosome 1 harboring CRB1. A subsequent CRB1 mutation analysis of the eight families, followed by screening of candidate founder mutations in the whole cohort of patients, revealed a total of 13 mutations, six of which are novel, in 15 families. Nine mutations were family-specific, and four were founder mutations identified in patients of Arab-Muslim origin, and Jews originated from Iraq and Kurdistan. Interestingly, a null mutation on at least one of the two mutated CRB1 alleles results in the LCA diagnosis, whereas patients carrying missense mutations were diagnosed with either RP or LCA. The average age at which CRB1 patients were referred to ERG testing was young (11 years). Of the 30 identified CRB1 patients, five had Coats-like exudative vasculopathy.
  
  
  CONCLUSIONS
  Our data show that CRB1 mutations are a relatively frequent cause of AR early-onset retinal degeneration in the Israeli and Palestinian populations (10% of LCA families), and causes severe retinal degeneration at an early age.
authors: Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors: Avigail
authors: A
authors: Beryozkin
authors: Lina
authors: L
authors: Zelinger
authors: Dikla
authors: D
authors: Bandah-Rozenfeld
authors: Anat
authors: A
authors: Harel
authors: Tim A
authors: TA
authors: Strom
authors: Saul
authors: S
authors: Merin
authors: Itay
authors: I
authors: Chowers
authors: Eyal
authors: E
authors: Banin
authors: Dror
authors: D
authors: Sharon
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D018912:Arabs / Q000208:ethnology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D007223:Infant; D007557:Israel / Q000453:epidemiology / Q000208:ethnology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012162:Retinal Degeneration / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D055815:Young Adult
chemical_list: C448939:CRB1 protein, human; D004268:DNA-Binding Proteins; D005136:Eye Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins