Mutations in the EPHA2 gene have been found to cause multiple types of cataract, which have been described as posterior polar, congenital total, complete, and age-related cortical.
The preferred title/symbol of this entry was formerly 'Cataract, ... Mutations in the EPHA2 gene have been found to cause multiple types of cataract, which have been described as posterior polar, congenital total, complete, and age-related cortical. The preferred title/symbol of this entry was formerly 'Cataract, posterior polar, 1; CTPP1,' and 'Cataract, Age-Related Cortical, 2; ARCC2' was formerly a distinct entry.
In Nettleship's family (Nettleship, 1909, 1912), congenital posterior polar opacities were present and scattered cortical opacities appeared in childhood and progressed to total cataract. Tulloh (1955) described 15 affected in 5 generations. Valk and Binkhorst (1956) described associated ... In Nettleship's family (Nettleship, 1909, 1912), congenital posterior polar opacities were present and scattered cortical opacities appeared in childhood and progressed to total cataract. Tulloh (1955) described 15 affected in 5 generations. Valk and Binkhorst (1956) described associated choroideremia and myopia in 2 generations. Ionides et al. (1997) reported 10 affected members of a family with autosomal dominant posterior polar cataract. The opacity, which was bilateral in all cases, consisted of a single well-defined plaque confined to the posterior pole of the lens and varied from 0.5 to 3 mm in diameter. Because of its proximity to the optical center of the eye, posterior polar cataract can have a marked effect on visual acuity. Hospital records indicated that the opacity was usually present at birth or developed within the first few months of life but did not progress with age to other regions of the lens. There was no evidence of posterior lenticonus or high myopia and no family history of other ocular or systemic abnormalities. McKay et al. (2005) studied a 6-generation Tasmanian family segregating autosomal dominant congenital cataract, previously studied by Burdon et al. (2004), in which most of the 13 patients were elderly and aphakic with no preoperative clinical notes available, although cataracts in 2 patients had been described as 'complete.' Most affected individuals were diagnosed shortly after birth, and the mean age of cataract surgery was 3 years, 4 months. Of the 12 aphakic patients, 11 had nystagmus, 2 had exotropia, 4 had esotropia, and 4 had bilateral aphakic glaucoma. One obligate carrier was phakic with good vision, but unavailable for slit-lamp examination. No other ocular or systemic abnormalities were noted in this family. Shiels et al. (2008) studied a 4-generation Caucasian family segregating autosomal dominant posterior polar cataracts with no systemic abnormalities. Ophthalmic records indicated that the cataracts usually presented in both eyes as disc-shaped posterior subcapsular opacities with evidence of posterior lenticonus. In 3 affected individuals, opacification progressed to affect the central (nuclear) and anterior polar regions of the lens. One affected individual also had monocular amblyopia, and 2 others developed strabismus requiring corrective surgery. Age at diagnosis ranged from birth to 15 years, and age at surgery ranged from 0 to 44 years; post-surgical corrected visual acuity varied from 20/20 to 20/70 in the better eye.
In a 4-generation Caucasian family with autosomal dominant posterior polar cataracts mapping to chromosome 1p36, Shiels et al. (2008) identified a heterozygous missense mutation in the EPHA2 gene (G948W; 176946.0001) that was not found in 192 controls. Candidate-gene ... In a 4-generation Caucasian family with autosomal dominant posterior polar cataracts mapping to chromosome 1p36, Shiels et al. (2008) identified a heterozygous missense mutation in the EPHA2 gene (G948W; 176946.0001) that was not found in 192 controls. Candidate-gene association analysis in a case-control cohort with age-related cortical and nuclear cataracts showed suggestive association with SNPs in the EPHA2 region of chromosome 1p (p less than 0.007 at dbSNP rs11260867 for cortical cataracts and p less than 0.01 at dbSNP rs7543472 for cortical and/or nuclear cataracts). In a 5-generation Han Chinese family segregating autosomal dominant posterior polar congenital cataract mapping to 1p36, Zhang et al. (2009) identified a heterozygous mutation in the EPHA2 gene (T940I; 176946.0002) that was present in all 7 affected family members but not detected in 6 unaffected family members or 202 unrelated Chinese controls. Zhang et al. (2009) then sequenced the EPHA2 gene in the British and Australian families with autosomal dominant cataract mapping to 1p, previously studied by Ionides et al. (1997) and McKay et al. (2005), respectively, and identified a heterozygous 2-bp deletion (176946.0003) and splice site mutation (176946.0004), respectively. In a large family with age-related cortical cataract, Jun et al. (2009) sequenced the EPHA2 gene and found that a nonsynonymous variant, R721Q (176946.0005), cosegregated with the phenotype. The frequency of the rare 'A' allele in 3 independent Caucasian study populations from the United States, United Kingdom, and Australia was 0.6%, 0%, and 0.2%, respectively; the authors stated that 0.1% to 0.2% probably represents a true population estimate for this rare variant. The risk allele had 78% penetrance in heterozygous individuals whose age was 70 years or more. Functional analysis demonstrated that R721Q significantly alters EPHA2 signaling and cellular regulation in vitro.