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R.H. Henderson, F. Ikeji, G. Holder, A.R. Webster, A.T. Moore; The Phenotypic Characteristics of Leber’s Congenital Amaurosis (LCA) Caused by Mutations in the CRB1 Gene . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1694.
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© ARVO (1962-2015); The Authors (2016-present)
To screen a large panel of DNA from patients with LCA and early onset retinal dystrophies examined at a single centre for mutations in the CRB1 gene and to carefully document the associated retinal phenotype.
DNA from patients with Leber’s Congenital Amaurosis (LCA) or Early Onset Retinal Dystrophies (EORD) were analyzed using the LCA microarray chip (Asper Bio) which identifies previously reported mutations in 6 LCA genes. All patients in whom a disease associated variant was found in CRB1 were subsequently screened by direct sequencing to confirm the mutation and in some cases identify the second allele. Patients in the study underwent full clinical examination, electroretinography and, where possible, Goldman visual fields, fundus photography, fundus autofluorescence imaging (FAF), OCT, biometry, keratometry and refraction.
DNA from100 patients were interrogated by the LCA chip. CRB1 mutations were identified in 12 patients. Direct sequencing has thus far verified all chip mutation calls and identified 3 novel mutations and one previously reported mutation not picked up by the chip.The visual acuity of children with CRB1 mutations acuities ranged from 0.7 Log Mar to light perception (average BCVA CF–HM). The refractive error of all but one patient was moderate hyperopia (mean +4.00 dioptres spherical equivalent) which correlates with short axial length (mean 19.26mm). Colour vision measured with the HRR colour test plates showed a severe generalised dyschromatopsia. There was a typical fundus appearance of widespread pigment clumping at the level of the RPE. A thickened retina on OCT was observed in all patients in whom it could be measured with an average foveal thickness of 271µm. Fundus autofluorescence imaging showed very low levels of autofluorescence. Electroretinography demonstrated absent retinal responses in all but three patients in whom small residual rod and cone responses were detected.
CRB1 mutations account for 12% of early onset retinal dystrophies in our cohort making it the commonest gene detected. There is a characteristic phenotype of severe visual loss, pigment clumping at the level of the RPE, reduced retinal autofluorescence and a thickened retina on OCT which may help identify those patients in whom screening of the CRB1 gene is appropriate.
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