Table 6.
Mutant connexin-43 domains and associated phenotype.
| GJA1 mutation | Protein domain (amino acid range) (obtained from UniProt-P17302) | Associated phenotype (no. of individuals) |
|---|---|---|
| p.G2fsX7 (with p.R101X) p.G2V p.L11P p.L11F p.L11I p.L7V p.S5C |
Cytoplasmic N-terminus(1-13) | Microcornea (7), microphthalmia (5), epicanthus (4), strabismus (3) (1 esotropic), short palpebral fissures (2), telecanthus (2), amblyopia (1), dysplastic fundus (1), optociliary vein (1), dysplastic optic disc (1), pale/atrophic optic disc (1), persistent pupillary membrane (1), myopia (3), hyperopia (1) (anisometropic), glaucoma (1), ptosis (1), entropion (1), madarosis (1), hypertelorism (1), and cataract (1) |
|
| ||
| p.W25C p. R33X p.I31M p.K23T p.G22E p.G21R p.S18P p.Y17S p.L26P |
Transmembrane-1 (14-36) | Microcornea (21), microphthalmia (14), short palpebral fissures (11), persistent pupillary membrane (6), madarosis (6), epicanthus (6), glaucoma (5), anterior iris stroma hypoplasia (3), hypertelorism (2), cataract (2), iris abnormalities (2), blonde fundus (1), iridoschisis (1), deep anterior chamber (1), hyperopia (2), strabismus (7) (3 esotropic), amblyopia (1), nystagmus (1), ptosis (1), epiblepharon (1), nasolacrimal duct obstruction (1), and flared eyebrows (1) (medially flared) |
|
| ||
| p.Q57SfsTer6 p.R76H p.R76C p.R76S p.H74P p.S69Y p.P59H p.Q49dup p.F52dup p.Q49P p.Q49E p.Q49K p.E48K p.D47H p.E42Q p.V41_A44del p.V41L (with p.R127H (GJB2 mutation)) p.A40V p.P59S |
Extracellular-1 (37-76) | Microphthalmia (32), microcornea (30), glaucoma (15) (2 closed-angle, 1 open-angle), hypertelorism (11), epicanthus (10), strabismus (9) (3 esotropic), short palpebral fissures (9), iris atrophy (peripupillary) (8), cataract (6), shallow anterior chamber (6), hypotelorism (5), short axial length (4), myopia (4), corneal farinata (4), telecanthus (3), iris abnormalities (2), eccentric pupils (2), persistent pupillary membrane (2), dysplastic fundus (1), dysplastic optic (1), macular hypoplasia (1), synechiae (1), ciliary body cysts (1), deep anterior chamber (1), hyperopia (1), ptosis (1), blepharophimosis (1), madarosis (1), nasolacrimal duct abnormalities (1), and low-voltage ERG (1) |
|
| ||
| p.Y98C p.V96A p.V96E p.V96M p.H95R p.L90V p.S86Y p.V96G |
Transmembrane-2 (77-99) | Hypertelorism (5), microcornea (2), microphthalmia (3), glaucoma (3), strabismus (2) (1 esotropic), short palpebral fissures (2), eyelid mucosal hypertrophy (1), telecanthus (1), epicanthus (1), optic disc atrophy (1), hyperopia (1), myopia (1), strabismus (1), paracentral scotoma (1), madarosis (1), and delayed visual evoked potentials (1) |
|
| ||
| p.R101X (with p.G2fsX7) p.R101X p.T154N p.T154A p.R148Q p.R148Ter p.M147T p.G143S p.G138D p.G138R p.G138S p.K134N p.K134E p.I130T p.L113P p.E110D p.L106R p.L106P p.K102N p.I132_K133delinsM |
Cytoplasmic-1 (100-154) | Microphthalmia (20), microcornea (18), short palpebral fissures (14), hypotelorism (14), glaucoma (9), myopia (7), epicanthus (5), cataract (3), strabismus (3), shallow anterior chamber (3), hypertelorism (2), opaque lens (1), optic disc hypervascularity (1), pale/atrophic optic disc (1), pale irides (1), iris abnormalities (2), astigmatism (1), Duane syndrome (1), ptosis (1), occipital subcortical white matter changes (1), and delayed visual evoked responses (1) |
|
| ||
| p.F169del | Transmembrane-3 (155-177) | Short palpebral fissures (1) |
|
| ||
| p.R202H (with p.R239R) p.R202H p.K206R p.S201F p.H194P |
Extracellular-2 (178-208) | Microphthalmia (18), uveitis (8), glaucoma (8), microcornea (4), opaque cornea (2), thick choroid (2), cataract (1), shallow anterior chamber (1), nystagmus (2), and ptosis (1) |
|
| ||
| p.S220Y p.V216L |
Transmembrane-4 (209-231) | Microphthalmia (1), glaucoma (1), microcornea (1), and persistent pupillary membrane (1) |
|
| ||
| p.Y230fsX236 | Transmembrane-4 & cytoplasmic C-terminus (209-382) | Hypertelorism (2), hypotelorism (1), and flared eyebrows (2) (1 medially flared) |
|
| ||
| p.R239R (with p.R202H) p.I311P p.C260fsX306 |
Cytoplasmic C-terminus(232-382) | Short palpebral fissures (3), epicanthus (2), hypotelorism (2), microcornea (2), pale irides (2), myopia (2), hyperopia (1) (1 anisometropic), corneal opacity (1), microphthalmia (1), retinal dysplasia (1), choroid thinning (1), glaucoma (1), madarosis (1), and loss of flash ERG (1) |
|
| ||
| Missense mutation exon 2 (unspecified) | Unknown | Microphthalmia (1), cataract (1), microcornea (1), uveitis (1), glaucoma (1), epicanthus (1), telecanthus (1), short palpebral fissures (1), and ptosis (1) |