title: A novel homozygous nonsense mutation in CABP4 causes congenital cone-rod synaptic disorder.
abstract: OBJECTIVE
  The purpose of this study was to identify the causative gene defect in two siblings with an uncharacterized cone-rod dysfunction and to describe the clinical characteristics.
  
  
  METHODS
  Genome-wide homozygosity mapping, with a 250K SNP-array followed by a search for candidate genes, was performed. The patients underwent ophthalmic examination, including elaborate electroretinography.
  
  
  RESULTS
  In a Dutch sib pair, a shared 9-Mb homozygous region was found on 11q13.1-q13.5 that encompasses the CABP4 gene, previously implicated in autosomal recessive incomplete congenital stationary night blindness (CSNB2) in two small families. A novel homozygous p.Arg216X mutation in CABP4 was detected in the sib pair. Quantitative RT-PCR on RNA isolated from patient lymphoblast cells showed no nonsense-mediated degradation of mutant CABP4 mRNA. Clinically, patients presented with reduced visual acuity, photophobia, and abnormal color vision, but they did not experience night blindness. Electroretinograms showed electronegative mixed rod-cone responses and severely reduced cone responses, as in CSNB2. Isolated rod responses, however, were (sub)normal.
  
  
  CONCLUSIONS
  A novel homozygous nonsense mutation in CABP4 in two siblings resulted in a phenotype with severely reduced cone function and only negligibly reduced rod function on electroretinography and psychophysical testing. Since these patients and two of three previously described patients do not experience night blindness, the name CSNB2 is confusing for patients as well as clinicians. Therefore, the authors propose to name the phenotype congenital cone-rod synaptic disorder.
authors.affiliation: Rotterdam Eye Hospital, Rotterdam, The Netherlands.
authors.forename: Karin W
authors.initials: KW
authors.lastname: Littink
authors.forename: Maria M
authors.initials: MM
authors.lastname: van Genderen
authors.forename: Rob W J
authors.initials: RW
authors.lastname: Collin
authors.forename: Susanne
authors.initials: S
authors.lastname: Roosing
authors.forename: Arjan P M
authors.initials: AP
authors.lastname: de Brouwer
authors.forename: Frans C C
authors.initials: FC
authors.lastname: Riemslag
authors.forename: Hanka
authors.initials: H
authors.lastname: Venselaar
authors.forename: Alberta A H J
authors.initials: AA
authors.lastname: Thiadens
authors.forename: Carel B
authors.initials: CB
authors.lastname: Hoyng
authors.forename: Klaus
authors.initials: K
authors.lastname: Rohrschneider
authors.forename: Anneke I
authors.initials: AI
authors.lastname: den Hollander
authors.forename: Frans P M
authors.initials: FP
authors.lastname: Cremers
authors.forename: L Ingeborgh
authors.initials: LI
authors.lastname: van den Born
mesh_terms: D002135:Calcium-Binding Proteins / Q000235:genetics*; D002648:Child; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D018389:Codon, Nonsense; D004596:Electroretinography; D005260:Female; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008297:Male; D009755:Night Blindness / Q000151:congenital / Q000175:diagnosis / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D010775:Photic Stimulation; D020419:Photoreceptor Cells, Vertebrate / Q000473:pathology*; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics; D012162:Retinal Degeneration / Q000151:congenital / Q000175:diagnosis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D035781:Siblings; D013569:Synapses; D058609:Visual Field Tests
chemical_list: C514441:CABP4 protein, human; D002135:Calcium-Binding Proteins; D018389:Codon, Nonsense; D012333:RNA, Messenger