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Genotype-phenotype correlation in a German family with a novel complex CRX mutation extending the open reading frame.
- Source :
-
Ophthalmology [Ophthalmology] 2007 Jul; Vol. 114 (7), pp. 1348-1357.e1. Date of Electronic Publication: 2007 Feb 22. - Publication Year :
- 2007
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Abstract
- Purpose: To describe the genotype-phenotype correlation in a German family with a novel CRX mutation and to perform a comparative analysis of published cases.<br />Design: Retrospective observational case series, systematic review, and comparative analysis of the literature.<br />Participants: Four related patients with progressive retinal degeneration.<br />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.<br />Main Outcome Measures: Visual fields, subjective and objective cone- and rod-specific function, fundus aspect, retinal stratification, and FA.<br />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.<br />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.
- Subjects :
- Adult
Aged
Color Perception Tests
Disease Progression
Electroretinography
Female
Fundus Oculi
Genotype
Heterozygote
Humans
Hyperopia etiology
Male
Night Blindness etiology
Nystagmus, Pathologic etiology
Pedigree
Phenotype
Retina pathology
Retinal Cone Photoreceptor Cells physiopathology
Retinal Degeneration complications
Retinal Degeneration diagnosis
Retinal Degeneration physiopathology
Retinal Rod Photoreceptor Cells physiopathology
Retrospective Studies
Tomography, Optical Coherence
Vision Disorders etiology
Visual Field Tests
Visual Fields
Homeodomain Proteins genetics
Mutation
Open Reading Frames genetics
Retinal Degeneration genetics
Trans-Activators genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1549-4713
- Volume :
- 114
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Ophthalmology
- Publication Type :
- Academic Journal
- Accession number :
- 17320181
- Full Text :
- https://doi.org/10.1016/j.ophtha.2006.10.034