title: A novel splice site mutation of CDHR1 in a consanguineous Israeli Christian Arab family segregating autosomal recessive cone-rod dystrophy.
abstract: OBJECTIVE
  To investigate the genetic basis for autosomal recessive cone-rod dystrophy in a consanguineous Israeli Christian Arab family.
  
  
  METHODS
  Patients underwent a detailed ophthalmic examination, including funduscopy, electroretinography (ERG), visual field testing, and optical coherence tomography. Genome-wide homozygosity mapping using a single nucleotide polymorphism array was performed to identify homozygous regions shared between the two affected individuals. Mutation screening of the underlying gene was performed with direct sequencing. In silico analysis was used to predict the effect of the mutation on splicing.
  
  
  RESULTS
  The family included two affected individuals. Clinical findings included progressive deterioration of visual acuity, photophobia, defective color vision, loss of central visual fields, pigmentary deposits localized mainly in the peripheral retina, a thinned and atrophic macular region, retinal vessel attenuation, absent ERG cone responses, and reduced ERG rod responses. Homozygosity mapping revealed several homozygous intervals shared among the affected individuals. One, a 12Mb interval on chromosome 10, included the CDHR1 gene. Direct sequencing revealed a single base transversion, c.1485+2T>G, located in the conserved donor splice site of Intron 13. This mutation cosegregated with the disease in the family, and was not detected in 208 Israeli Christian Arab control chromosomes. In silico analysis predicted that this mutation eliminates the Intron 13 donor splice site.
  
  
  CONCLUSIONS
  Only three distinct pathogenic mutations of CDHR1 have been reported to date in patients with autosomal recessive retinal degeneration. Here we report a novel splice site mutation of CDHR1, c.1485+2T>G, underlying autosomal recessive cone-rod dystrophy in a consanguineous Israeli Christian Arab family. This report expands the spectrum of pathogenic mutations of the CDHR1 gene.
authors.affiliation: The Rappaport Family Institute for Research in the Medical Sciences, Haifa, Israel.
authors.forename: Ben
authors.initials: B
authors.lastname: Cohen
authors.forename: Elena
authors.initials: E
authors.lastname: Chervinsky
authors.forename: Haneen
authors.initials: H
authors.lastname: Jabaly-Habib
authors.forename: Stavit A
authors.initials: SA
authors.lastname: Shalev
authors.forename: Daniel
authors.initials: D
authors.lastname: Briscoe
authors.forename: Tamar
authors.initials: T
authors.lastname: Ben-Yosef
mesh_terms: D000328:Adult; D018912:Arabs; D000070585:Cadherin Related Proteins; D015820:Cadherins / Q000235:genetics*; D016022:Case-Control Studies; D003241:Consanguinity; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005260:Female; D005808:Genes, Recessive; D006720:Homozygote; D006801:Humans; D007438:Introns; D007557:Israel; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D022821:RNA Splice Sites; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism* / Q000473:pathology; D012174:Retinitis Pigmentosa / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D058609:Visual Field Tests
chemical_list: C442481:CDHR1 protein, human; D000070585:Cadherin Related Proteins; D015820:Cadherins; D009419:Nerve Tissue Proteins; D022821:RNA Splice Sites