Table 1 Patients with likely causative variants.

From: Revealing hidden genetic diagnoses in the ocular anterior segment disorders

Patient number

Inheritance before/after testing

Phenotype

Platform

Gene (NM)

Nucleotide change (heterozygous, except where otherwise specified)

Amino acid change

gnomAD MAF

In silico: SIFT, MutTaster, PolyPhen, PhyloP (respectively)

ACMG criteria

Segregation

Novel

1

Spor/new AD

IH & PA

Array

FOXC1 NM_001453.2

chr6 del :1595464–1716115

n/a

n/a

n/a

n/a

De novo

No

2

Spor/new AD

ARS

Array

PITX2 NM_153427.1

chr4 del: 111445336–112392782

n/a

n/a

n/a

n/a

De novo

No

5

Spor/new AD

Sclero

ES

GJA8 NM_005267.4

c.281G>A

p.(Gly94Glu)

Nil

D, D, P, highly conserved

LP (PM2, PM6, PP2, PP3)

De novo

No

9

Spor/AR

ARA

ES

ADAMTS17 NM_139057.2

hom c.526C>T

p.(Arg176*)

Nil

n/a

P (PVS1, PM2, PM4)

Segregates

Yes

10

Spor/Fam (AD)

ARA

ES

FOXC1 NM_001453.2

c.516_518dupGCG

p.(Arg173dup)

Nil

n/a

LP (PM1, PM2, PP1, PP3)

Segregates

Yes

11

Fam (AD)/AD

PA

GS CNV

PAX6 NM_000280.4

del chr11:31822357–31823717

n/a

n/a

n/a

n/a

Segregates

Yes

12

Fam (AD)/AD

ARA

ES

FOXC1 NM_001453.2

c.518G>A

p.(Arg173His)

Nil

D, D, P, highly conserved

LP (PM1, PM2, PP2, PP3)

Segregates

Yes

14

Spor/likely new AD

ARA

ES

PITX2 NM_153427.1

c.341dup

p.(Asn115Glnfs*84)

Nil

n/a

P (PVS1, PM2, PM4)

n/k

Yes

15

Spor/new AD

Sclero

ES

GJA8 NM_005267.4

c.280G>C

p.(Gly94Arg)

Nil

D, D, P, highly conserved,

LP (PM2, PM6, PP2, PP3)

De novo

No

19

Spor/likely new AD

ARS

ES

PITX2 NM_153427.1

c.250C>T

p.(Arg84Trp)

Nil

D, D, P, highly conserved

P (PS1, PM1, PM2, PP2, PP3)

n/k

No

21

Spor/AR

Sclero

ES

PXDN NM_012293.2

Hom c.4085_4086delAG

p.(Gln1362Argfs*22)

1/249,252 (het only)

n/a

P (PVS1, PM2, PM4)

n/k

No

23

Spor/likely new AD

PA

ES

FOXC1 NM_001453.2

c.1399C>T

p.(Gln467*)

Nil

n/a

P (PVS1, PM2, PM4)

n/k

Yes

25

Spor/new AD

IH

GS trio

ITPR1 NM_001168272.1

c.7615G>A

p.(Gly2539Arg)

1/249,244 (het only)

D, D, P, highly conserved

LP (PS1, PM2, PP2, PP3)

De novo

No

26

Spor/Fam (AD)

PA

ES

COL4A1 NM_001845.5

c.634G>A

p.(Gly212Ser)

Nil

D, D, P, highly conserved

LP (PM1, PM2, PP2, PP3)

Segregates

No

28

Spor/AR

ARA

GS trio

CPAMD8 NM_015692.2

Comp Het c.4549–1G>A

Splice p.(=)

1/249,494 (het only)

n/a

P (PVS1, PS3, PM2, PP5)

Segregates (mat)

No

     

c.3149G>T

p.(Gly1050Val)

1/249,372 (het only)

D, D, P, highly conserved

LP (PM2, PM3, PP2, PP3)

Segregates (pat)

Yes

29

Spor/AR

PA

ES

CYP1B1 NM_000104.3

Hom c.171G>A

p.(Trp57*)

42/233,224 (het only)

n/a

P (PVS1, PM2, PM4)

n/k

No

30

Spor/AR

PA

ES

CYP1B1 NM_000104.3

Comp Het c.171G>A;

p.(Trp57*)

42/233,224 (het only)

n/a

P (PVS1, PM2, PM4)

n/k

No

     

c.1331G>A

p.(Arg444Gln)

Nil

D, D, P, highly conserved

P (PS3, PM2, PM3, PP1, PP5)

n/k

No

32

Fam(AD)/fam (AR)

Multiple ASD

GS

FOXE3 NM_012186.2

Hom c.720C>A

p.(Cys240*)

7/43,132 (het only)

n/a

P (PVS1, PS3, PM2, PPS5)

Segregates

No

36

Spor/likely new AD

Sclero

GS

PITX2 NM_153427.1

c.185G>A

p.(Arg62His)

Nil

D, D, P, highly conserved

P (PS1, PM1, PM2, PP2, PP3)

n/k

No

38

Spor/AR

PA

ES

CYP1B1 NM_000104.3

Comp Het c.171G>A

p.(Trp57*)

21/50,846 (het only)

n/a

P (PVS1, PM2, PM4)

Segregates

No

     

c.1200_1209dup

p.(Thr404Serfs*30)

Nil

n/a

P (PVS1, PM2, PM4)

Segregates

No

39

Spor/new AD

PA

ES

PAX6 NM_000280.4

c.152G>T

p.(Gly51Val)

Nil

D, D, P, highly conserved

LP (PM2, PM6, PP2, PP3)

De novo

No

41

Spor/new AD

IH

ES

FOXC1 NM_001453.2

c.478_482dup

p.(Met161Ilefs*22)

Nil

n/a

P (PVS1, PM2)

De novo

Yes

  1. Human genome reference GRCh37/HG19 used and NCBI gene reference sequences (NM) provided. gnomAD database v2.1.1 was used (https://gnomad.broadinstitute.org/). ACMG criteria according to ref. 9 References for previously published variants also included in table. In Silico: D, damaging; P, pathogenic.
  2. ACMG American College of Medical Genetics and Genomics, AD autosomal dominant, AR autosomal recessive, ARA Axenfeld–Rieger anomaly, ARS Axenfeld–Rieger syndrome, ASD anterior segment disorder, ES exome sequencing, Fam familial, GS genome sequencing, Het heterozygous, Hom homozygous, IH iris hypoplasia, LP likely pathogenic, MAF minor allele frequency, P pathogenic, PA Peters anomaly, Sclero sclerocornea, Spor sporadic.
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