A number sign (#) is used with this entry because of evidence that Leber congenital amaurosis-16 (LCA16) is caused by homozygous mutation in the KCNJ13 gene (603208) on chromosome 2q37.

For a general phenotypic description and a discussion of genetic heterogeneity of Leber congenital amaurosis, see LCA1 (204000).

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 (SD-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.

Khan et al. (2015) reported 2 unrelated Saudi Arabian probands with vitreoretinal dystrophy and early-onset cataract. Both patients exhibited fine pendular nystagmus, and their retinas had an unusual dystrophic appearance, with fibrosis over the disc into the posterior vitreous, deep clumped pigmentation in the posterior pole, and relative sparing of the periphery. Electroretinography (ERG) in both revealed severe cone-rod dysfunction, with no recordable cone function and only minimally delayed and depressed scotopic readings recordable. The first proband was a 12-year-old girl who had poor vision and nystagmus noted soon after birth, with worse vision at night. Examination showed photophobia, with a best-corrected visual acuity of hand motion in the right eye, in which she had a total white cataract, and 20/100 in the left eye, where there were posterior lenticular changes. At cataract surgery, the anterior capsule was unusually thick and inelastic. The proband had a younger sister with a diagnosis of nonsyndromic congenital retinal dystrophy; examination was difficult due to uncooperativeness, but showed sunken globes with oculodigital sign, photophobia, nystagmus, and small angle esotropia, as well as attenuated vessels and disc pallor. Their first-cousin parents and 2 brothers were unaffected. The second proband was a 33-year-old man from a consanguineous Saudi Arabian family in which he and 3 of his 10 sibs had early childhood-onset retinal dystrophy. The proband, who presented because of recent decreased vision, had a best-corrected visual acuity of 20/400 in both eyes. Visually significant central anterior and posterior cataracts were present bilaterally; visually insignificant bilateral posterior lens opacities had been noted at age 20 years. Khan et al. (2015) stated that the fundus appearance of the 2 probands was remarkably similar to that of the 2 brothers reported by Sergouniotis et al. (2011), and noted that the 2 brothers also developed early adult-onset cataract.

Pattnaik et al. (2015) studied a 10-year-old boy of Jordanian descent who presented with a history of night vision difficulties from the age of 2 years and poor central vision at school age. At age 8 years, his best-corrected visual acuity was 20/200 in the right eye and 20/400 in the left eye. Fundus examination revealed RPE mottling in the macula of both eyes, as well as arteriolar attenuation. Examination at age 10 showed that visual acuity had deteriorated to 20/400 on the right and 'count fingers' on the left. Retinal examination confirmed arteriolar abnormalities, pigmentation of the retina in the macular region, and bilateral RPE abnormalities. On OCT, the retina appeared intact; however, SD-OCT revealed degeneration of the outer retina, with only 1 high-contrast band visualized. There were clearly visible areas of hypertrophy in the choroidal structure, and small sub-RPE focal deposits were also present.

In a consanguineous Middle Eastern family with Leber congenital amaurosis, Sergouniotis et al. (2011) performed genomewide homozygosity mapping and identified 4 chromosomal segments, of which the largest was a 45-cM interval between SNPs rs10192834 and rs10199178 on chromosome 2q.

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).

In a 12-year-old Saudi Arabian girl with vitreoretinal dystrophy and early-onset cataract, Khan et al. (2015) analyzed 87 early-onset retinal dystrophy-associated genes and identified homozygosity for a missense mutation in the KCNJ13 gene (I120T; 603208.0004). The mutation segregated with disease in the family. Sequencing of KCNJ13 in a 33-year-old Saudi Arabian man with similar ocular findings revealed homozygosity for the same I120T mutation. Because both probands had recordable ERGs, at age 12 and 33 years, respectively, Khan et al. (2015) suggested that 'early-onset vitreoretinal degeneration with early-onset cataract' would be a more appropriate designation than Leber congenital amaurosis.

In a 10-year-old boy of Jordanian descent with Leber congenital amaurosis, Pattnaik et al. (2015) analyzed a panel of LCA-associated genes and identified homozygosity for a nonsense mutation in the KCNJ13 gene (W53X; 603208.0005). His unaffected parents were heterozygous for the mutation.