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.
|Number of pages||9|
|Journal||Investigative ophthalmology & visual science|
|Publication status||Published - Nov 2010|
- AC133 Antigen
- ATP-Binding Cassette Transporters/genetics
- Amino Acid Sequence
- Antigens, CD/genetics
- Calcium-Binding Proteins/genetics
- Chromosome Mapping
- DNA Mutational Analysis
- Eye Proteins/genetics
- Fluorescein Angiography
- Middle Aged
- Molecular Sequence Data
- 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