Roosing et al. (2013) studied a German family in which 3 sibs were diagnosed with cone-rod dystrophy in the second decade of life, with rapidly deteriorating visual acuities and high myopia. Funduscopy showed hyperpigmentation of the fovea, and ... Roosing et al. (2013) studied a German family in which 3 sibs were diagnosed with cone-rod dystrophy in the second decade of life, with rapidly deteriorating visual acuities and high myopia. Funduscopy showed hyperpigmentation of the fovea, and autofluorescence revealed a slightly hyperfluorescent fovea. Optical coherence tomography (OCT) showed altered photoreceptors in the fovea but intact peripheral photoreceptors. Color-vision tests revealed defects in all axes, and visual field testing showed a central scotoma. On electroretinography (ERG), photopic responses were nondetectable and scotopic responses reduced in all 3 sibs. Roosing et al. (2013) also studied a consanguineous family of Moroccan Jewish origin in which a brother and sister with CORD had a presentation similar to that of the sibs from the German family. The brother presented with low vision from early childhood, with progressive deterioration of visual acuity and high myopia. The retinal pigment epithelium showed foveal atrophy; hypofluorescence was observed in the fovea and a hyperfluorescent ring was noted around the fovea. OCT imaging confirmed absence of photoreceptors in the central fovea, whereas the photoreceptor layer further out appeared largely intact. Color-vision defects were noted in both sibs. Photopic ERG responses were nondetectable, and scotopic responses were moderately reduced.
In 2 of 3 affected sibs from a German family with CORD, Roosing et al. (2013) performed exome sequencing but found no pathogenic variants in known autosomal recessive CORD-associated genes among the shared variants; there was only a ... In 2 of 3 affected sibs from a German family with CORD, Roosing et al. (2013) performed exome sequencing but found no pathogenic variants in known autosomal recessive CORD-associated genes among the shared variants; there was only a single homozygous shared variant, a nonsense mutation in the RAB28 gene (E189X; 612994.0001), located within the largest shared homozygous region in the family. Sanger sequencing confirmed homozygosity for the mutation in the 3 affected sibs, and it was not found in 176 ethnically matched controls or in the Exome Variant Server database (release ESP6500). Sequencing of RAB28 in 468 CORD probands and 149 probands with cone dystrophy revealed no mutations. Analysis of SNP data from more than 400 probands in the European Retinal Disease Consortium, including patients with autosomal recessive CORD, Leber congenital amaurosis (see 204000), and retinitis pigmentosa (see 268000) identified 7 families with large homozygous regions spanning RAB28; Sanger sequencing of RAB28 in those families revealed a homozygous nonsense mutation (R137X; 612994.0002) in affected sibs from a consanguineous family of Moroccan Jewish ancestry with CORD.