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Joseph F Griffith, Meghan J Marino, Elias I Traboulsi; A Novel CRX Mutation in a Family with Findings Suggestive of Benign Concentric Annular Macular Dystrophy. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2868.
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© ARVO (1962-2015); The Authors (2016-present)
To present the phenotype of a mother and son initially given a diagnosis of benign concentric annular macular dystrophy (BCAMD) and later found to have a novel nonsense mutation in the cone-rod homeobox (CRX) gene (19q13.3).
Patients underwent complete ophthalmic examinations. The son underwent sequencing of 131 retinal dystrophy genes. His mother was tested for the presence of the discovered sequence variations in two potentially causative genes CRX and BBS12 (4q27).
The son (Case I) presented at age 35 years for routine eye care. He had a family history of multiple males and females with early onset retinal disease. Over nine years of follow-up, his visual acuity (VA) remains at 20/20 - 20/25 in each eye with normal color vision. Ophthalmoscopy shows peripapillary atrophy and a bull’s eye macular lesion. His mother (Case II) presented at age 57 years with unilateral, progressive vision loss for nine months. She reported a prior VA of 20/30 in the right eye and on examination was 20/400 in that eye. Over five years of follow-up, VA fluctuated from 20/100 - 20/400 in the right eye and remains 20/25 in the left eye with decreased color vision (1/11, Ishihara Color Test). Ophthalmoscopy is similar to Case I except for a smaller area of preserved central retina. Fundus autofluorescence shows parafoveal hypofluorescence and an outer ring of hyperfluorescence. OCT demonstrates atrophy of the outer retina, subretinal excrescences, and segmental loss of the ellipsoid layer and the retinal pigment epithelium. BCAMD was the working diagnosis because of the characteristic retinal lesion, preserved VA, and presumed autosomal dominant inheritance. Genetic testing identified a novel nonsense mutation in CRX (p.Gln256stop:c.766C>T) in both patients. The son was also heterozygous for a missense mutation in BBS12 (p.Gln620Arg:c.1859A>G), which was not present in Case II.
CRX mutations are associated with cone-rod dystrophy 2, Leber congenital amaurosis 7, retinitis pigmentosa, cone dystrophy, and a recently described adult-onset macular dystrophy. Genetic studies of the original BCAMD family demonstrated linkage to 6p12.3-q16 and no mutations in CRX. There is wide clinical heterogeneity resulting from CRX mutations, including phenotypes characterized by a bull’s eye retinal lesion and fairly well preserved visual acuity.
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