Purchase this article with an account.
Sarah Hull, Gavin Arno, Sarah Chamney, Isabelle Russell-Eggitt, Anthony G Robson, Graham E Holder, Andrew Webster, Anthony T Moore; Phenotypic variability of retinal dystrophies associated with mutations in CRX: with report of a novel macular dystrophy phenotype. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3279.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
To present the detailed clinical and molecular features of a series of patients with retinal dystrophies consequent upon mutations in the cone-rod homeobox (CRX) gene.
Eighteen patients from 11 families with retinal dystrophies and CRX mutations were identified; 7 from a large genetics database, 3 from results of exome analysis and 8 by direct sequencing of CRX in a selected panel of 65 cases. Detailed phenotyping included full clinical evaluation, electrophysiological testing, fundus photography, fundus autofluorescence imaging and optical coherence tomography. Bi-directional Sanger sequencing of all exons and intron-exon boundaries of CRX was performed on all 18 patients and available relatives.
Eleven of 18 patients had generalized photoreceptor dysfunction and 7 had late onset macular dystrophy. Five families had more than 1 affected family member and within 3 families, significant phenotypic heterogeneity was found. Four patients presented in infancy with severe visual loss, featureless fundi, macular atrophy in 2 cases, and an undetectable ERG. Two patients presented aged 3 and 6 with reduced vision, evidence of severe retinal dysfunction rod more than cone on electroretinogram (ERG) and progressive deterioration to severe loss of vision by their mid-teens. Five patients presented 11-25 years old with reduced central vision and cone dysfunction greater than rod on ERG. Seven patients from 5 families presented with a bulls eye macular dystrophy at age 35-50 years. Electrophysiology showed an abnormal pattern ERG in all cases. The full field ERG showed reduced cone responses in 1 case and mild rod and cone dysfunction in 2 cases. Visual acuities at last review ranged from 0.2 to 1.3 logMAR. All 18 patients were heterozygous for a rare, likely disease-causing variant in CRX. Eight novel mutations were identified. A de novo mutation was confirmed in 3 families. There was no clear association between the severity, or age of onset and the type or position of CRX mutation.
Mutations in CRX demonstrate significant phenotypic heterogeneity both between and within pedigrees. A novel, late onset, predominantly macular dystrophy is described, extending the phenotypic spectrum associated with mutations in CRX.
This PDF is available to Subscribers Only