Genotype-phenotype correlation in a German family with a novel complex CRX mutation extending the open reading frame.
OBJECTIVE
To describe the genotype-phenotype correlation in a German family with a novel CRX mutation and to perform a comparative analysis of published cases.


METHODS
Retrospective observational case series, systematic review, and comparative analysis of the literature.


METHODS
Four related patients with progressive retinal degeneration.


METHODS
Mutation screening by single-strand polymorphism analysis and direct sequencing. Clinical examination included kinetic visual fields (VFs), 2-color threshold perimetry (2CTP), full-field electroretinography, fundus photography, optical coherence tomography, and fundus autofluorescence (FA) recording.


METHODS
Visual fields, subjective and objective cone- and rod-specific function, fundus aspect, retinal stratification, and FA.


RESULTS
A novel heterozygous complex mutation (c.816delCACinsAA) in CRX predicting the substitution of 27 C-terminal amino acids by 44 novel amino acids, thus abolishing the OTX tail, was identified in a 2-generation family finally diagnosed with cone-rod dystrophy (CRD), which was confirmed by 2CTP. Patients presented with variability in progression, nystagmus, and nyctalopia. Most of the patients were hyperopic. Electroretinography recordings showed residual rod and mixed cone-rod responses in 2 of the subjects. Age-dependent VF losses followed funduscopic changes of progressive atrophy of the retinal pigment epithelium and neuroretina in the macula and midperiphery marked by disturbed FA. Optical coherence tomography showed decreased central retinal thickness. Comparative analysis of the 131 published data sets revealed 2 groups: patients with early and late onset.


CONCLUSIONS
We described a 2-generation family with a novel mutation in CRX. The resulting phenotype is that of CRD with variable age at onset and progression. The phenotype description of previously published cases is conclusive only for CRD.
Paunescu
K
K
Department of Pediatric Ophthalmology, Strabismology, and Ophthalmogenetics, Klinikum, University of Regensburg, Regensburg, Germany.
Preising
M N
MN
Janke
B
B
Wissinger
B
B
Lorenz
B
B
D000328:Adult; D000368:Aged; D003119:Color Perception Tests; D018450:Disease Progression; D004596:Electroretinography; D005260:Female; D005654:Fundus Oculi; D005838:Genotype; D006579:Heterozygote; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D006956:Hyperopia / Q000209:etiology; D008297:Male; D009154:Mutation; D009755:Night Blindness / Q000209:etiology; D009759:Nystagmus, Pathologic / Q000209:etiology; D016366:Open Reading Frames / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D012160:Retina / Q000473:pathology; D017949:Retinal Cone Photoreceptor Cells / Q000503:physiopathology; D012162:Retinal Degeneration / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D017948:Retinal Rod Photoreceptor Cells / Q000503:physiopathology; D012189:Retrospective Studies; D041623:Tomography, Optical Coherence; D015534:Trans-Activators / Q000235:genetics*; D014786:Vision Disorders / Q000209:etiology; D058609:Visual Field Tests; D014794:Visual Fields
D018398:Homeodomain Proteins; D015534:Trans-Activators; C109288:cone rod homeobox protein