Table 2.
FOXC1 mutations and ocular and hearing phenotypes
| Protein variant | Protein domain | cDNA variant | Hearing Phenotype | Ocular Phenotype | Reference |
|---|---|---|---|---|---|
| Q2X | Active 1 | c.4C>T | NR | ARA | Komatireddy et al., 2003 |
| R4fs | Active 1 | c.12delC | NR | Glaucoma | Chakrabarti et al., 2009 |
| S9fsX89 | Active 1 | c.26–47ins | Deafness | Iris hypoplasia, corectopia | Kawase et al., 2001 |
| Q23X | Active 1 | c.67C>T | Hearing loss | ARA, glaucoma | Mirzayans et al., 2001 |
| R28_30del | Active 1 | c.81_89del9 | NR | Glaucoma | Chakrabarti et al., 2009 |
| A31_33del | Active 1 | c.92_100del9 | NR | Glaucoma | Kaur et al., 2009 |
| A31fsX41 | Active 1 | c.93_102del10 | No systemic findings | ARA, glaucoma | Michael et al., 2016 |
| A31fsX41 | Active 1 | c.93_102del10 | No systemic findings | ARA, glaucoma | Mears et al., 1998 |
| G33fsX41 | Active 1 | c.99_108del10 | NR | ARA | Nishimura et al., 2001 |
| G34fsX8 | Active 1 | c.100_109del10 | NR | PE, glaucoma | Souzeau et al., 2017 |
| A39fsX42 | Active 1 | c.116_123del8 | NR | ARA | Nishimura et al., 2001 |
| Y47X | Active 1 | c.141C>G | NR | Glaucoma | Medina-Trillo et al., 2015 |
| S48X | Active 1 | c.143C>A | No systemic findings | PE, corectopia | Weisschuh et al., 2006 |
| A51fsX73 | Active 1 | c.153_163del11 | NR | ARA, glaucoma | Nishimura et al., 1998 |
| Y64X | After Active 1 |
c.192C>G | NR | ARA, glaucoma | Carmona et al., 2017 |
| Q70fsX73 | Forkhead | c.210delG | Hearing loss | ARA, glaucoma | Swiderski RE et al. 1999 |
| P79T | Forkhead | c.235C>A | Hearing loss | ARA, glaucoma | Suzuki T et al., 2001 |
| P79R | Forkhead | c.236C>G | NR | Iris hypoplasia, glaucoma | Weisschuh et al., 2006 |
| P79L | Forkhead | c.236C>T | NR | ARA | Saleem et al., 2003 |
| P79L | Forkhead | c.236C>T | NR | ARA | Nishimura et al., 1998 |
| S82T | Forkhead | c.245G>C | Hearing loss | ARA, glaucoma | Mears et al., 1998 |
| A85P | Forkhead | c.253G>C | NR | ARA, glaucoma | Fuse et al., 2007 |
| L86F | Forkhead | c.256C>T | NR | ARA, glaucoma | Saleem et al., 2003 |
| I87M | Forkhead | c.261C>G | No systemic findings | ARA, glaucoma | Mears et al., 1998 |
| T88fsX100 | Forkhead | c.262_265insC | NR | ARA | Nishimura et al., 2001 |
| A90T | Forkhead | c.268G>A | No systemic findings | PE, glaucoma | Souzeau et al., 2017 |
| A90D | Forkhead | c.269C>A | NR | Glaucoma | Siggs et al., 2019 |
| I91S | Forkhead | c.272T>G | NR | ARA, glaucoma | Kawase et al., 2001 |
| I91T | Forkhead | c.272T>C | NR | ARA | Mortemousque et al.,2004 |
| D96GfsX210 | Forkhead | c.286dupG | NR | PE, glaucoma | D’Haene et al., 2011 |
| D96fsX305 | Forkhead | c.286insG | NR | ARA, glaucoma | Kawase et al., 2001 |
| Q106X | Forkhead | c.316C>T | NR | ARA, glaucoma | D’Haene et al., 2011 |
| Q106X | Forkhead | c.316C>T | NR | ARA, glaucoma | Souzeau et al., 2017 |
| Q106RfsX75 | Forkhead | c.317delA | Normal hearing | ARA, glaucoma | Kim et al., 2013 |
| M109V | Forkhead | c.325A>G | Hearing loss | Corectopia | D’Haene et al., 2011 |
| F112SfsX69 | Forkhead | c.335del | Hearing Loss | ARA, glaucoma | D’Haene et al., 2011 |
| F112S | Forkhead | c.335T>C | NR | ARA, glaucoma | Nishimura et al., 1998 |
| F112S | Forkhead | c.335T>C | NR | ARA, glaucoma | Honkanen et al., 2003 |
| Y115S | Forkhead | c.339T>C | Middle-ear deafness | ARA, glaucoma | Weisschuh et al., 2006 |
| D117TfsX64 | Forkhead | c.349delG | NR | ARA, glaucoma | Siggs et al., 2019 |
| Q120X | Forkhead | c.358C>T | NR | ARA, glaucoma | Weisschuh et al., 2008 |
| Q123X | Forkhead | c.367C>T | NR | ARA, glaucoma | Komatireddy et al., 2003 |
| I126M | Forkhead | c.378C>G | NR | ARA, glaucoma | Nishimura et al., 1998 |
| H128R | Forkhead | c.378A>G | NR | Glaucoma | Chakrabarti et al., 2009 |
| R127H | Forkhead | c.380G>A | NR | ARA, glaucoma | Kawase et al., 2001 |
| R127L | Forkhead | c.380T>G | NR | ARA, glaucoma | Du et al., 2016 |
| L130F | Forkhead | c.388C>T | NR | ARA, glaucoma | Ito et al., 2007 |
| S131L | Forkhead | c.392C>T | NR | ARA, glaucoma | Nishimura et al., 1998 |
| S131X | Forkhead | c.392C>A | NR | Glaucoma | D’Haene et al., 2011 |
| S131W | Forkhead | c.392C>G | NR | ARA | D’Haene et al., 2011 |
| C135Y | Forkhead | c.402G>A | NR | Glaucoma | Chakrabarti et al., 2009 |
| V137del | Forkhead | c.409_411del | NR | PE, glaucoma | Siggs et al., 2019 |
| K138E | Forkhead | c.412A>G | NR | PE, glaucoma | D’Haene et al., 2011 |
| P146fs | Forkhead | c.437_453del17 | Hearing loss | ARA, glaucoma | Fuse et al., 2007 |
| G149D | Forkhead | c.446G>A | NR | ARA, glaucoma | Weisschuh et al., 2006 |
| W152R | Forkhead | c.454T>C | Mild deafness | ARA, glaucoma | Michael et al., 2016 |
| W152G | Forkhead | c.454T>G | NR | Glaucoma | Ito et al., 2009 |
| W152X | Forkhead | c.456G>A | NR | ARA, glaucoma | Cella et al., 2006 |
| T153P | Forkhead | c.457A>C | Hearing loss | PE, glaucoma | Siggs et al., 2019 |
| M161V | Forkhead | c.481A>G | Middle-ear deafness | ARA, glaucoma | Weisschuh et al., 2006 |
| M161K | Forkhead | c.482T>A | NR | ARA, glaucoma | Panicker et al., 2002 |
| M161K | Forkhead | c.482T>A | NR | ARA, glaucoma | Komatireddy et al., 2003 |
| E163X | Forkhead | c.487G>T | Hearing Loss | Glaucoma | Siggs et al., 2019 |
| G165R | Forkhead | c.494G>C | NR | ARA, glaucoma | Murphy et al., 2004 |
| R169P | Forkhead | c.506G>C | Hearing loss | ARA | Murphy et al., 2004 |
| R170W | Forkhead | c.508C>T | Hearing Loss | ARA, glaucoma | Gripp et al., 2013 |
| Q200fsX109 | After Forkhead |
c.599_617del19 | NR | ARA | Souzeau et al., 2017 |
| P202RfsX113 | After Forkhead |
c.605delC | NR | ARA, glaucoma | D’Haene et al., 2011 |
| A204RfsX111 | After Forkhead |
c.609delC | NR | ARA, glaucoma | Kelberman et al., 2011 |
| I223PfsX87 | Inhibitory | c.666_681del16 | NR | PE glaucoma | Souzeau et al., 2017 |
| G231VfsX73 | Inhibitory | c.692_696del5 | NR | ARA, glaucoma | D’Haene et al., 2011 |
| L240VfsX65 | Inhibitory | c.718_719delCT | No systemic findings | ARA, glaucoma | Cella et al., 2006 |
| L240VfsX65 | Inhibitory | c.718_719delCT | NR | Glaucoma | Siggs et al., 2019 |
| L240RfsX75 | Inhibitory | c.719delT | + | Glaucoma | Hariri et al.,2018 |
| L246fsX68 | Inhibitory | c.738delG | NR | Iris atrophy, glaucoma | Weisschuh et al., 2006 |
| D261RfsX45 | Inhibitory | c.780dup | NR | NR | D’Haene et al., 2011 |
| S272RfsX43 | Inhibitory | c.816_817delinsG | NR | NR | D’Haene et al., 2011 |
| A291fs | Inhibitory | c.853dup25 | NR | Glaucoma | Chakrabarti et al., 2009 |
| P297S | Inhibitory | c.889C>T | NR | Glaucoma | Fetterman et al., 2009 |
| P297S | Inhibitory | c.889C>T | NR | Glaucoma | Medina-Trillo et al., 2016 |
| S309CfsX84 | Inhibitory | c.925_949del25 | NR | Glaucoma | Souzeau et al., 2017 |
| E327AfsX200 | Inhibitory | c.980_981del | NR | NR | D’Haene et al., 2011 |
| G379Gins | After Inhibitory |
c.1142_1144insGGC | No systemic findings | Iris atrophy, glaucoma | Yang et al., 2015 |
| M400SfsX129 | After inhibitory |
c.1193_1196dup | Congenital deafness | Iris atrophy, glaucoma | Reis et al., 2016 |
| S422X | After Inhibitory |
c.1265C>A | NR | ARA, glaucoma | Souzeau et al., 2017 |
| G452insR | After Inhibitory |
c.1362_1364insCGG | No systemic findings | Iris atrophy, glaucoma | Yang et al., 2015 |
| Y497X | Active 2 | c.1491C>G | NR | Glaucoma | D’Haene et al., 2011 |
| Y497X | Active 2 | c.1491C>G | Hearing Loss | PE, glaucoma | Souzeau et al., 2017 |
| N503fsX15 | Active 2 | c.1511delT | NR | ARA, glaucoma | Weisschuh et al., 2006 |
| F504fsX518 | Active 2 | c.1512delG | NR | ARA | Nishimura et al., 2001 |
Abbreviations: ARA, Axenfeld-Rieger anomaly; PE, Posterior embryotoxon; NR = Not reported.