Table 2.
Summary of disease-associated alleles in FOXE3.
| Mode | DNA effecta | Protein effect | Phenotype | Functional prediction | gnomAD frequency | Reference |
|---|---|---|---|---|---|---|
| REC | c.21_24delGG AT | p.(Met7Ilefs*216) | Microphthalmia, aphakia, sclerocornea, ASD | Premature truncation | 1/65338 (0.002%) | (Iseri et al. 2009) |
| VUS | c.146G>C | p.(Gly49Ala) | Microphthalmia, coloboma | Damaging by 1/5 (F) | 361/26504 (1.4%); 355/8250 African (4.3%); 5 homozygotes |
(Iseri et al. 2009) |
| REC | c.232G>A | p.(Ala78Thr) | Microphthalmia, sclerocornea | Damaging by 5/5 (S, PP, F, MA, MT) | NP | (Plaisancie et al. 2017) |
| REC | c.244A>G | p.(Met82Val) | Microphthalmia, sclerocornea, aphakia, ASD | Damaging by 5/5 (S, PP, F, MA, MT) | 24/259912 (0.009%) | (Iseri et al. 2009) |
| DOMb REC | c.269G>T | p.(Arg90Leu) | Peters anomaly Aphakia, corneal opacity | Damaging by 5/5 (S, PP, F, MA, MT) | 24/268362 (0.009%) | (Ormestad et al. 2002) (Islam et al. 2015) |
| DOMb REC | c.289A>G | p.(Ile97Val) | Cataract, syndromic Microphthalmia, corneal opacity | Damaging by 5/5 (S, PP, F, MA, MT) | 5/243212 (0.002%) | (Gillespie et al. 2014; Ullah et al. 2016) (Ullah et al. 2016) |
| REC | c.292T>C | p.(Tyr98His) | Sclerocornea, non-syndromic, bilateral, total | Damaging by 5/5 (S, PP, F, MA, MT) | NP | (Ali et al. 2010) |
| REC | c.307G>A | p.(Glu103Lys) | Congenital cataract | Damaging by 4/5 (S, PP, F, MT) | 1/29030 (0.003%) | (S. Y. Khan et al. 2016) |
| REC | c.310C>T | p.(Arg104Cys) | Microphthalmia, sclerocornea | Damaging by 5/5 (S, PP, F, MA, MT) | 1/244576 (0.0004%) | (Plaisancie et al. 2017) |
| REC | c.345G>A | p.(Trp115*) | Microphthalmia, sclerocornea | Premature truncation | NP | (Plaisancie et al. 2017) |
| REC | c.351C>G | p.(Asn117Lys) | Congenital cataract | Damaging by 5/5 (S, PP, F, MA, MT) | NP | (S. Y. Khan et al. 2016) |
| REC | c.358C>G | p.(Arg120Gly) | Aphakia, corneal opacity | Damaging by 5/5 (S, PP, F, MA, MT) | 1/245968 (0.0004%) | (Islam et al. 2015) |
| REC | c.387C>G | p.(Phe129Leu) | Abnormality of the eye | Damaging by 5/5 (S, PP, F, MA, MT) | NP | (Retterer et al. 2016) |
| DOM | c.410G>A | p.(Gly137Asp) | Thoracic aortic aneurysms and dissections | Damaging by 4/5 (S, PP, F, MT) | 6/244140 (0.002%) | (Kuang et al. 2016) |
| DOM | c.457G>C | p.(Asp153His) | Thoracic aortic aneurysms and dissections | Damaging by 4/5 (S, PP, F, MT) | 1/29224 (0.003%) | (Kuang et al. 2016) |
| DOM | c.466G>A | p.(Asp156Asn) | Thoracic aortic aneurysms and dissections | Damaging by 5/5 (S, PP, F, MA, MT) | 76/262358 (0.03%) | (Kuang et al. 2016) |
| REC | c.472G>C | p.(Gly158Arg) | Microphthalmia, aphakia, staphyloma malformation | Damaging by 5/5 (S, PP, F, MA, MT) | 1/29234 (0.003%) | (Saboo et al. 2017) |
| DOM | c.490C>A | p.(Arg164Ser) | Thoracic aortic aneurysms and dissections | Damaging by 4/5 (PP, F, MA, MT) | NP | (Kuang et al. 2016) |
| REC | c.557delT | p.(Phe186Serfs*38) | Microphthalmia, aphakia, sclerocornea | Premature truncation | NP | (Reis et al. 2010) |
| VUS | c.601G>A | p.(Val201Met) | Possible risk factor for eye malformations | Damaging by 1/5 (F) | 272/86326 (0.3%); 236/5842 Hispanic (4.0%); 7 homozygotes | (Garcia-Montalvo et al. 2014) |
| REC | c.679_686dup | p.(Ala230Argfs*3) | Microphthalmia, sclerocornea | Premature truncation | NP | (Chassaing et al. 2014) |
| REC | c.705delC | p.(Glu236Serfs*71) | Microphthalmia, aphakia, sclerocornea | Premature truncation | NP | (Reis et al. 2010) |
| REC | c.720C>A | p.(Cys240*) | Microphthalmia, aphakia, sclerocornea | Premature truncation | 7/42902 (0.02%) | (Valleix et al. 2006) |
| DOM | c.942dupG | p.(Leu315Alafs*117) | Anterior segment ocular dysgenesis and cataracts | Erroneous extension | NP | (Semina et al. 2001) |
| DOM | c.958T>C | p.(*320Argext*72) | Cataract, ASD, unilateral micro | Erroneous extension | NP | (Iseri et al. 2009) |
| DOM | c.959G>C | p.(*320Serext*72) | Cataract, congenital | Erroneous extension | NP | (Bremond-Gignac et al. 2010) |
| DOM | c.959G>T | p.(*320Leuext*72) | Anterior segment dysgenesis | Erroneous extension | NP | (Doucette et al. 2011) |
a
Reference sequence: NM_012186.2; Non-ocular anomalies indicated in italics
b
Heterozygous alleles also reported in unaffected individuals
DOM, Dominant; REC, Recessive; VUS, heterozygous variant of uncertain significance reported as causative/associated in at least one paper; PP, Polyphen2; S, SIFT; F, FATHMM; MA, Mutation Assessor; MT, Mutation Taster; NP, Not Present