TABLE 2.

The genotype and phenotype of ARS patients with PITX2 mutations.

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
22/F/2y	Yes	Iridocorneal adhesions, severe IH, corectopia, polycoria, GL	DA; CA	c.103A > T	p.K35X	Nonsense	NA	Familial; Father + Mother-	P	Novel
23/F/12y	No	PE, iridocorneal adhesions, IH, polycoria, myopia	DA; UA	c.155A > C	p.Q52P	Missense	Damaging/PD/Deleterious	Sporadic; Father- Mother-	LP	Novel
24/M/38y	No	PE, iridocorneal adhesions, IH, irregular pupil, GL, cataract	DA	c.158_173GGTAGCT	p.E53_V271delinsG	Nonsense	NA	Sporadic; Father/Mother/	P	Novel
25/F/10m	No	Iridocorneal adhesions, severe IH, irregular pupil, GL	DA; CA	c.173T > G	p.F58C	Missense	Damaging/PD/Deleterious	Sporadic; Father/Mother/	LP	Novel
26/F/49y	No	Iridocorneal adhesions, IH, corectopia, GL, corneal opacification (OD)	DA; CA	c.173T > C	p.F58S	Missense	Damaging/PD/Deleterious	Sporadic; Father/Mother/	LP	Novel
27/M/17y	Yes	PE, iridocorneal adhesions, IH, corectopia, GL, high myopia, cataract	DA; surgery history for umbilical hernia	c.190C > G	p.P64A	Missense	Damaging/PD/Deleterious	Familial; Father + Mother/	LP	Novel
28/M/34y	No	PE, IH, corectopia, GL	DA	c.253–11A > G	NA	Splicing	NA	Sporadic; Father/Mother/	VUS	Ref Semina et al. (1996)
29/F/46y	Yes	PE, iridocorneal adhesions, IH, corectopia, GL, cataract	DA	c.253–11A > G	NA	Splicing	NA	Familial; Father/Mother/	VUS	Ref Semina et al. (1996)
30/M/24y	No	Iridocorneal adhesions, severe IH, corectopia, irregular pupil, GL	DA; CA	c.253-1G > A	NA	Splicing	NA	Sporadic; Father- Mother-	P	Ref Reis et al. (2012)
31/F/5y	Yes	PE, iridocorneal adhesions, severe IH, corectopia, irregular pupil, GL, corneal opacification, high myopia	CA	c.269G > C	p.R90P	Missense	Damaging/PD/Deleterious	Familial; Father- Mother+	VUS	Ref Phillips (2002)
32/M/64y	Yes	PE, iridocorneal adhesions, IH, corectopia, GL, high myopia, cataract	DA; UA	c.282G > A	p.W94X	Nonsense	NA	Familial; Father/Mother/	LP	Ref D’Haene et al. (2011)
33/M/12y	No	Iridocorneal adhesions, IH, corectopia, polycoria, GL, high myopia	DA; CA; surgery history for umbilical hernia	c.348delG	p.L117Sfs*37	Deletion	NA	Sporadic; Father/Mother/	P	Novel
34/M/24y	Yes	PE, iridocorneal adhesions, IH, polycoria	DA	c.377delC	p.P126Qfs*28	Deletion	NA	Familial; Father/Mother/	P	Novel
35/M/34y	No	PE, iridocorneal adhesions, IH, corectopia, polycoria, ectropion uvea, GL, high myopia	DA; kidney stone	c.539_551del	p.M180Kfs*1	Deletion	NA	Sporadic; Father/Mother/	P	Novel

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

^bPITX2 variants were analyzed according to transcript NM_153427.2. Novel variants are shown in bold.

Abbreviations: ACMG, American College of Medical Genetics and Genomics; CA, Craniofacial abnormalities; DA, Dental abnormalities; F, Female; GL, Glaucoma; IH, Iris hypoplasia; LP, Likely pathogenic; M, Male; NA, Not applicable; OD, Right eye; P, Pathogenic; PD, Probably damaging; PE, Posterior embryotoxon; UA, Umbilical anomalies; VUS, Variant of uncertain significance; +, positive for the variant; − , negative for the variant; / , not available for testing.