title: Homozygosity mapping in patients with cone-rod dystrophy: novel mutations and clinical characterizations.
abstract: OBJECTIVE
  To determine the genetic defect and to describe the clinical characteristics in a cohort of mainly nonconsanguineous cone-rod dystrophy (CRD) patients.
  
  
  METHODS
  One hundred thirty-nine patients with diagnosed CRD were recruited. Ninety of them were screened for known mutations in ABCA4, and those carrying one or two mutations were excluded from further research. Genome-wide homozygosity mapping was performed in the remaining 108. Known genes associated with autosomal recessive retinal dystrophies located within a homozygous region were screened for mutations. Patients in whom a mutation was detected underwent further ophthalmic examination.
  
  
  RESULTS
  Homozygous sequence variants were identified in eight CRD families, six of which were nonconsanguineous. The variants were detected in the following six genes: ABCA4, CABP4, CERKL, EYS, KCNV2, and PROM1. Patients carrying mutations in ABCA4, CERKL, and PROM1 had typical CRD symptoms, but a variety of retinal appearances on funduscopy, optical coherence tomography, and autofluorescence imaging.
  
  
  CONCLUSIONS
  Homozygosity mapping led to the identification of new mutations in consanguineous and nonconsanguineous patients with retinal dystrophy. Detailed clinical characterization revealed a variety of retinal appearances, ranging from nearly normal to extensive retinal remodeling, retinal thinning, and debris accumulation. Although CRD was initially diagnosed in all patients, the molecular findings led to a reappraisal of the diagnosis in patients carrying mutations in EYS, CABP4, and KCNV2.
authors.affiliation: The Rotterdam Eye Hospital, Rotterdam, The Netherlands.
authors.forename: Karin W
authors.initials: KW
authors.lastname: Littink
authors.forename: Robert K
authors.initials: RK
authors.lastname: Koenekoop
authors.forename: L Ingeborgh
authors.initials: LI
authors.lastname: van den Born
authors.forename: Rob W J
authors.initials: RW
authors.lastname: Collin
authors.forename: Luminita
authors.initials: L
authors.lastname: Moruz
authors.forename: Joris A
authors.initials: JA
authors.lastname: Veltman
authors.forename: Susanne
authors.initials: S
authors.lastname: Roosing
authors.forename: Marijke N
authors.initials: MN
authors.lastname: Zonneveld
authors.forename: Amer
authors.initials: A
authors.lastname: Omar
authors.forename: Mahshad
authors.initials: M
authors.lastname: Darvish
authors.forename: Irma
authors.initials: I
authors.lastname: Lopez
authors.forename: Hester Y
authors.initials: HY
authors.lastname: Kroes
authors.forename: Maria M
authors.initials: MM
authors.lastname: van Genderen
authors.forename: Carel B
authors.initials: CB
authors.lastname: Hoyng
authors.forename: Klaus
authors.initials: K
authors.lastname: Rohrschneider
authors.forename: Mary J
authors.initials: MJ
authors.lastname: van Schooneveld
authors.forename: Frans P M
authors.initials: FP
authors.lastname: Cremers
authors.forename: Anneke I
authors.initials: AI
authors.lastname: den Hollander
mesh_terms: D000071916:AC133 Antigen; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000293:Adolescent; D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000235:genetics; D002135:Calcium-Binding Proteins / Q000235:genetics; D002648:Child; D002874:Chromosome Mapping; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005451:Fluorescein Angiography; D006023:Glycoproteins / Q000235:genetics; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D009887:Ophthalmoscopy; D010455:Peptides / Q000235:genetics; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics; D020419:Photoreceptor Cells, Vertebrate / Q000473:pathology*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics; D012174:Retinitis Pigmentosa / Q000175:diagnosis / Q000235:genetics*; D041623:Tomography, Optical Coherence
chemical_list: C056475:ABCA4 protein, human; D000071916:AC133 Antigen; D018528:ATP-Binding Cassette Transporters; D015703:Antigens, CD; C514441:CABP4 protein, human; D002135:Calcium-Binding Proteins; C533105:EYS protein, human; D005136:Eye Proteins; D006023:Glycoproteins; C489610:KCNV2 protein, human; C000606023:PROM1 protein, human; D010455:Peptides; D024642:Potassium Channels, Voltage-Gated; D017853:Phosphotransferases (Alcohol Group Acceptor); C066324:ceramide kinase