Sergouniotis et al. (2011) studied a consanguineous Middle Eastern family in which 2 brothers had nystagmus at birth and were diagnosed with Leber congenital amaurosis shortly thereafter. Poor night vision and difficulty reading print from an early age ... Sergouniotis et al. (2011) studied a consanguineous Middle Eastern family in which 2 brothers had nystagmus at birth and were diagnosed with Leber congenital amaurosis shortly thereafter. Poor night vision and difficulty reading print from an early age was reported for both patients; gradual progression of visual problems affecting central and peripheral vision was also noted. Both patients had bilateral cataract surgery in their third decade. Funduscopy revealed significant pigment in the retinal pigment epithelium (RPE), in a configuration unlike that of typical retinitis pigmentosa (see 268000). There was no other family history of retinal disease. Sergouniotis et al. (2011) also studied a 33-year-old man of European descent who was noted to have strabismus, nystagmus, and poor vision before 1 year of age and was diagnosed with LCA at age 2 years. Only mild progression was reported, with night vision having most noticeably deteriorated. He was moderately myopic and underwent bilateral cataract surgery in his early twenties. Examination showed bilateral nystagmus and severe field loss with relative preservation of the inferior field. Funduscopy revealed areas of nummular pigment in the RPE, especially over the posterior pole. In vivo cross-sectional imaging by spectral domain optical coherence tomography (OCT) revealed loss of outer retinal structures, thinning of the hyperreflective band corresponding to RPE/Bruch membrane, and a coarse lamination pattern. Noting the distorted retinal microanatomy in an area of the fundus in which cell death was not evident, Sergouniotis et al. (2011) suggested that this might represent disturbance of the early development of the neurosensory retina.
In a consanguineous Middle Eastern family with Leber congenital amaurosis mapping to chromosome 2q, Sergouniotis et al. (2011) performed targeted exome sequencing of a 38-Mb target region of chromosome 2q and identified homozygosity for a nonsense mutation in ... In a consanguineous Middle Eastern family with Leber congenital amaurosis mapping to chromosome 2q, Sergouniotis et al. (2011) performed targeted exome sequencing of a 38-Mb target region of chromosome 2q and identified homozygosity for a nonsense mutation in the KCNJ13 gene (603208.0002) that segregated with disease in the family. The authors then analyzed the KCNJ13 gene in 132 additional unrelated patients with recessive LCA or childhood-onset retinal dystrophy who were negative for mutation in known LCA genes as well as 201 patients diagnosed with autosomal recessive adult-onset rod/cone dystrophy, and in a 33-year-old man of European descent with a phenotype 'remarkably similar' to that of the Middle Eastern family, they identified homozygosity for a missense mutation in KCNJ13 (603208.0003).