TABLE 1.

The genotype and phenotype of ARS patients with FOXC1 mutations or gross deletions of 6p25.

No./Sex/Diagnosis age	Family history a	Ocular manifestation	Systemic manifestation	Nucleotide changes b	Amino acid changes	Tape of mutation	SIFT/PolyPhen2/Provean	Segregation	ACMG category	Previous literature
1/M/15y	Yes	PE, iridocorneal adhesions, IH, corectopia, GL	—	c.205delC	p.P69Rfs*8	Frameshift	NA	Familial; Father/Mother/Brother+	P	Novel
2/F/22y	No	PE, iridocorneal adhesions, GL, high myopia	CHD	c.236C > T	p.P79 L	Missense	Damaging/PD/Deleterious	Sporadic; Father/Mother-	LP	Ref Nishimura et al. (2001)
3/M/4m	No	PE, iridocorneal adhesions, IH, GL (OD), corneal opacification (OD)	—	c.240_241insTAT	p.Y81_S82insY	Insertion	NA	Sporadic; Father/Mother+	P	Novel
4/F/14y	Yes	PE, iridocorneal adhesions, IH, corectopia, GL	—	c.246C > G	p.S82R	Missense	Damaging/PD/Deleterious	Familial; Father + Mother/	LP	Novel
5/M/5y	No	PE, IH, corectopia, polycoria, GL, nystagmus, amblyopia	—	c.247T > C	p.Y83H	Missense	Damaging/PD/Deleterious	Sporadic; Father- Mother-	LP	Novel
6/M/7m	No	PE, iridocorneal adhesions, corectopia, GL, CLDO	—	c.257T > C	p.L86P	Missense	Damaging/PD/Deleterious	Sporadic; Father- Mother-	LP	Novel
7/M/12y	No	PE, iridocorneal adhesions, IH, GL, keratoconus, corneal decompensation, cataract	—	c.275A > C	p.Q92P	Missense	Damaging/PD/Deleterious	Sporadic; Father- Mother-	LP	Novel
8/M/7m	No	PE, iridocorneal adhesions, IH, GL, corneal decompensation	CHD	c.364T > G	p.W122G	Missense	Damaging/PD/Deleterious	Sporadic; Father + Mother/	VUS	Novel
9/M/1m	Yes	PE, iridocorneal adhesions, IH, ectropion uvea, GL	—	c.380G > A	p.R127H	Missense	Damaging/PD/Deleterious	Familial; Father- Mother+	LP	Ref Kawase et al. (2001)
10/F/3m	Yes	PE, iridocorneal adhesions, GL, corneal decompensation	—	c.380G > A	p.R127H	Missense	Damaging/PD/Deleterious	Familial; Father + Mother-	LP	Ref Kawase et al. (2001)
11/M/1m	No	PE, iridocorneal adhesions, GL, corneal opacification	—	c.388C > T	p.L130F	Missense	Damaging/PD/Deleterious	Sporadic; Father- Mother-	P	Ref Strungaru et al. (2007)
12/M/1m	Yes	Iridocorneal adhesions, ectropion uvea, GL, corneal opacification	CHD	c.392C > T	p.S131L	Missense	Damaging/PD/Deleterious	Familial; Father + Mother/	LP	Ref Nishimura et al. (1998)
13/F/15y	Yes	PE, iridocorneal adhesions, GL	—	c.399C > G	p.N133K	Missense	Damaging/PD/Deleterious	Familial; Father- Mother/	VUS	Novel
14/F/9y	Yes	PE, iridocorneal adhesions, IH, GL, corneal opacification	—	c.430A > T	p.K144X	Nonsense	NA	Familial; Father- Mother/	LP	Novel
15/M/15y	Yes	PE, iridocorneal adhesions, IH, corectopia, polycoria, ectropion uvea, GL	—	c.482T > A	p.M161K	Missense	Damaging/PD/Deleterious	Familial; Father/Mother/	VUS	Ref Panicker et al. (2002)
16/F/8m	No	PE, iridocorneal adhesions, GL, corneal opacification	—	c.513_518del	p.R172_R173del	Deletion	NA	Sporadic; Father + Mother-	P	Novel
17/M/2m	Yes	Iridocorneal adhesions, IH, corectopia, polycoria, GL	—	c.592_593delinsC	p.G198Pfs*117	Frameshift	NA	Familial; Father + Mother/	P	Novel
18/F/18y	Yes	PE, iridocorneal adhesions, GL	—	c.718_719del	p.L240Vfs*64	Frameshift	NA	Familial; Father/Mother + Sister+	P	Ref Cella et al. (2006)
19/F/40y	No	PE, iridocorneal adhesions, GL, ectropion uvea	Hearing loss	c.1540delC	p.Q514Rfs*4	Frameshift	NA	Sporadic; Father/Mother/	P	Novel
20/F/2m	No	PE, iridocorneal adhesions, GL, corneal opacification	CA	Gross deletion in 6:1478641–2694750	NA	Deletion	NA	Sporadic; Father/Mother/	P	Novel
21/M/5m	Yes	PE, iridocorneal adhesions, GL	CHD; GD; hydrocephalus	Gross deletion in 6:382441–2333070	NA	Deletion	NA	Familial; Father/Mother/	P	Novel

^aNote: Family history refers to first-degree relatives having glaucoma or ARS.

^bFOXC1 variants were analyzed according to transcript NM_001453.2. Novel variants are shown in bold.

Abbreviations: ACMG, American College of Medical Genetics and Genomics; CA, Craniofacial abnormalities; CLDO, Congenital nasolacrimal duct obstruction; CHD, Congenital heart disease; F, Female; GD, Growth disorder; GL, Glaucoma; IH, Iris hypoplasia; LP, Likely pathogenic; M, Male; NA, Not applicable; OD, Right eye; P, Pathogenic; PD, Probably damaging; PE, Posterior embryotoxon; VUS, Variant of uncertain significance; + , positive for the variant; − , negative for the variant; / , not available for testing.