Homozygosity mapping in patients with cone-rod dystrophy: novel mutations and clinical characterizations

Karin W Littink, Robert K Koenekoop, L Ingeborgh van den Born, Rob W J Collin, Luminita Moruz, Joris A Veltman, Susanne Roosing, Marijke N Zonneveld, Amer Omar, Mahshad Darvish, Irma Lopez, Hester Y Kroes, Maria M van Genderen, Carel B Hoyng, Klaus Rohrschneider, Mary J van Schooneveld, Frans P M Cremers, Anneke I den Hollander

Research output: Contribution to journalArticleResearchpeer-review


PURPOSE: 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.

Original languageEnglish
Pages (from-to)5943-51
Number of pages9
JournalInvestigative ophthalmology & visual science
Issue number11
Publication statusPublished - Nov 2010


  • AC133 Antigen
  • ATP-Binding Cassette Transporters/genetics
  • Adolescent
  • Amino Acid Sequence
  • Antigens, CD/genetics
  • Calcium-Binding Proteins/genetics
  • Child
  • Chromosome Mapping
  • Consanguinity
  • DNA Mutational Analysis
  • Eye Proteins/genetics
  • Female
  • Fluorescein Angiography
  • Glycoproteins/genetics
  • Homozygote
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Mutation
  • Ophthalmoscopy
  • Peptides/genetics
  • Phosphotransferases (Alcohol Group Acceptor)/genetics
  • Photoreceptor Cells, Vertebrate/pathology
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide
  • Potassium Channels, Voltage-Gated/genetics
  • Retinitis Pigmentosa/diagnosis
  • Tomography, Optical Coherence


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