Table 2 of
Haghighi, Mol Vis 2012; 18:211-218. Table 2 of
Haghighi, Mol Vis 2012; 18:211-218.
Table 2. Natural FOXL2 missense mutations outside the forkhead domain reported to date in BPES: clinical and molecular genetic data, in silico predictions and in vitro studies.
| FOXL2 mutation (nucleotide level) | FOXL2 mutation (protein level) |
Phenotype |
Clinical data |
In silico predictions (conservation, Grantham distance, Polyphen, SIFT) |
Subcellular distribution of mutant FOXL2-GFP |
Transactivation properties of mutant FOXL2-GFP |
|---|---|---|---|---|---|---|
| c.644A>G | p.Tyr215Cys (p.Y215C) [19]. | BPES familial | Mild BPES (no epicanthus inversus, no broad and low nasal bridge, normal visual acuity) in five generation Indian family. BPES type could not be assessed. Co-segregation of mutation with disease. | Conservation: high up to Opossum (considering 11 species). Grantham distance: 194. Polyphen: probably damaging. SIFT: affect protein function (deleterious). | Intranuclear aggregation (p<0.001 in comparison with wild type protein) [14]. | Similar transactivation capacities compared to wild type protein (4xFLRE-luc and SIRT1-luc constructs) [14]. |
| c.650C>T | p.Ser217Phe (p.S217F) [12]. | BPES familial | Mild BPES. Co-segregation of mutation with disease. | Conservation: moderate (considering 11 species). Grantham distance: 155. Polyphen: possibly damaging. SIFT: affect protein function (deleterious) | No impairment compared to wild type [12]. | Increased transactivation compared to wild type using DK3 promotor [12]. Classified as type II mutations using 4xFLRE-luc and SIRT1-luc constructs [14]. |
| c.650C>G | p.Ser217Cys (p.S217C) [13]. | BPES familial | Mild BPES | Conservation: moderate (considering 11 species). Grantham distance: 112. Polyphen: possibly damaging. SIFT: tolerated | No impairment compared to wild type [13]. | No change compared to wild type [13]. Classified as type II mutations using 4xFLRE-luc and SIRT1-luc constructs [14]. |
| c.650C>G | p.Ser217Cys (p.S217C). This study. | BPES familial (type 2) | Severe BPES. Co-segregation of mutation with disease. | See above | See above | See above |