MRC Human Genetics Unit LOVD at MRC IGMM Paired box gene 6 (PAX6)	LOVD v.2.0 Build 30 [ Current LOVD status ] | Log in
	Curators: Graeme Grimes, Isabel Hanson, Kathy Williamson and Veronica van Heyningen

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This database has been closed to new submissions.

The date of last curation was 07 June 2017 and the 'last update' on 04 August 2018 was a partial and uncurated update.

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About this overview [Show] The variants below are all in the PAX6 database. All fields are shown, including patient and pathogenicity information. A '+' in the DNA change field indicates that more variants were found in this patient. Variants reported in a gene database other than PAX6, are reported as the gene symbol with the number of reported variants between parenthesis. Selecting and clicking a specific line will open a detailed view showing all details per patient. At the bottom of this page a legend is provided with a short explanation of what each field contains. For a more detailed description of each field, please see the PAX6 full legend here.

879 public entries
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Path.	Exon	Location	Legacy DNA ID	DNA change	RNA change	Protein change	RNA information	Protein information	DB-ID	Base number	5' Sequence Context	Original Sequence	Variant Sequence	3' Sequence Context	Type	Domain	Detection Method	RE Site	Frequency	Remarks	Patient ID	Disease	Reference/Submitter	Template	Technique	Remarks	# Reported	Population	Gender	Sequence Inheritance	Phenotype Inheritance	Second PCR	CIS	Conserved residue	Related Phenotype	Unrelated  Phenotype

+/+

-

Whole gene

PAX6 deletion

chr11:18,536,224-31,923,308

r.0

p.0

All exons missing - no transcription

-

PAX6_00888

-

-

-

-

-

Deletion

-

CGH

-

-

Whole gene deletion (13.9 Mb), also detected by MLPA

Blanco-Kelly 2017

Aniridia

Blanco-Kelly et al 2017 [28231309], Spain:Madrid

DNA

CGH

Whole gene deletion (13.9 Mb), also detected by MLPA

1

Spanish

female

de novo

Sporadic

-

-

-

Syndromic aniridia

-

+/+

-

Whole gene

PAX6 deletion

chr11:21,254,000-32,564,000del

r.0

p.0

All exons missing - no transcription

-

PAX6_00869

-

-

-

-

-

Deletion

-

CGH

-

-

Whole gene deletion also detected by FISH

1851

Aniridia

[27124303], United Kingdom (Great Britain):Edinburgh

DNA

CGH

-

1

-

-

-

-

-

-

-

-

-

+/+

-

Whole gene

PAX6 deletion

chr11:21,586,131-33,168,232

r.0

p.0

All exons missing - no transcription

-

PAX6_00890

-

-

-

-

-

Deletion

-

CGH

-

-

Whole gene deletion (11.6 Mb), also detected by STR analysis

Blanco-Kelly 2017

Aniridia

Blanco-Kelly et al 2017 [28231309], Spain:Madrid

DNA

CGH

Whole gene deletion (11.6 Mb), also detected by STR analysis

1

Spanish

male

de novo

Sporadic

-

-

-

Aniridia and developmental delay. No Wilms tumour

-

+/+

-

Whole gene

PAX6 deletion

chr11:29,750,813-32,752,091

r.0

p.0

All exons missing - no transcription

-

PAX6_00884

-

-

-

-

-

Deletion

-

CGH

-

-

Whole gene deletion (3Mb) also validated by MLPA

Blanco-Kelly 2017

Aniridia

Blanco-Kelly et al 2017 [28231309], Spain:Madrid

DNA

CGH

Whole gene deletion (3Mb) also detected by MLPA

1

Spanish

female

de novo

Sporadic

-

-

-

WAGR syndrome

-

+/+

-

Whole gene

PAX6 deletion

chr11:31,199,000-31,849,000del

r.0

p.0

All exons missing - no transcription

-

PAX6_00870

-

-

-

-

-

Deletion

-

CGH

-

-

Whole gene deletion (650kb) also detected by FISH

2193

Aniridia

[27124303], United Kingdom (Great Britain):Edinburgh

DNA

CGH

-

1

-

female

-

Familial

-

-

-

Aniridia

-

+/+

-

Whole gene

PAX6 deletion

chr11:31,394,000-31,914,000del

r.0

p.0

All exons missing - no transcription

-

PAX6_00871

-

-

-

-

-

Deletion

-

CGH

-

-

Whole gene deletion 520kb

377

Aniridia

[27124303], United Kingdom (Great Britain):Edinburgh

DNA

CGH

-

1

-

female

-

-

-

-

-

-

-

+/+

-

Whole gene

PAX6 deletion

chr11:31,698,271-31,794,414del

r.0

p.0

All exons missing - no transcription

-

PAX6_00873

-

-

-

-

-

Deletion

-

CGH

-

-

Whole gene deletion (96kb)

1977

Aniridia

[27124303], United Kingdom (Great Britain):Edinburgh

DNA

CGH

-

1

-

female

-

Familial

-

-

-

Bilateral aniridia, cataract

-

+/+

-

Whole gene

PAX6 deletion

chr11:31,779,000-31,933,000del

r.0

p.0

All exons missing - no transcription

-

PAX6_00872

-

-

-

-

-

Deletion

-

CGH

-

-

Whole gene deletion 154kb

1510

Aniridia

[27124303], United Kingdom (Great Britain):Edinburgh

DNA

CGH

-

1

-

female

-

-

-

-

-

-

-

+/+

-

Whole gene

PAX6 deletion

del(11)(p12p14.2)

r.0

p.0

All exons missing - no transcription

-

PAX6_00867

-

-

-

-

-

Deletion

-

Other

-

-

Whole gene deletion detected by cytogenetic analysis

Patient 25

Aniridia

[27081561], United Kingdom (Great Britain):Edinburgh

DNA

Other

Deletion detected by cytogenetic analysis

1

-

female

-

Sporadic

-

-

-

Total aniridia, cataract, foveal hypoplasia. No mental retardation. No Wilms’ tumour

-

+/+

-

Whole gene

PAX6 deletion

del(11)(p13p14)

r.0

p.0

All exons missing - no transcription

-

PAX6_00868

-

-

-

-

-

Deletion

-

Other

-

-

Whole gene deletion detected by cytogenetic analysis

Patient 26

Aniridia

[27081561], United Kingdom (Great Britain):Edinburgh

DNA

Other

Deletion detected by cytogenetic analysis

1

-

male

-

Sporadic

-

-

-

Total aniridia, cataract, foveal hypoplasia. No mental retardation. No Wilms’ tumour

-

+/+

-

-

-

Deletion of exons 5 and 6

-

-

-

-

PAX6_00842

-

-

-

-

-

Deletion

-

CGH

-

-

-

1002

Aniridia

[26661695], United Kingdom (Great Britain):Edinburgh

DNA

CGH

-

1

-

female

-

Sporadic

-

-

-

-

-

+/+

-

-

-

Deletion P1 promoter to exon 4

-

-

-

-

PAX6_00841

-

-

-

-

-

Deletion

-

CGH

-

-

-

228

Aniridia

[26661695], United Kingdom (Great Britain):Edinburgh

DNA

CGH

-

1

-

male

-

Sporadic

-

-

-

-

-

+/+

1-5

-

-

chr11:31,780,904_31,789,463del

-

-

Exons 1-5 missing

-

PAX6_00708

-

-

-

-

-

Deletion

-

MLPA

-

-

8.5 kb deletion of exons 1-5

-

Congenital aniridia

Russian Federation:Moscow

DNA

MLPA

-

1

Crimea Tatar

female

de novo

Sporadic

-

no

-

OU partial aniridia, microcornea, macular hypoplasia, normal lens

-

?/?

02

Exon

c.225del13

-138_-129+3del13

r.spl?

p.?

Exon/intron junction deleted - probable splice error

Outcome unknown without RNA analysis

PAX6_00502

1

AGGATG

CCTCATAAAG/GTG

-

AGTCCG

Deletion

-

DHPLC

-

-

-

284

Aniridia

[18241071], United Kingdom (Great Britain):Edinburgh

DNA

DHPLC

-

1

-

-

-

Sporadic

Y

-

-

-

-

?/?

02

Intron

IVS2+2T>A

c.-129+2T>A

r.spl?

-

Predicted abolition of intron 2 splice donor. Outcome unknown

Effect on protein unknown

PAX6_00400

-

TAAAG/G

T

A

GAGTCC

-

-

DHPLC

-

-

-

n/a

Atypical Gillespie Syndrome

[17148041], United Kingdom (Great Britain):Edinburgh

DNA

DHPLC

Gillespie syndrome is characterised by iris hypoplasia ('partial aniridia'), cerebellar ataxia and mental retardation. This patient does not have ataxia and may therefore have a variant PAX6 phenotype. It is unclear if the mild neurological anomalies are associated with the PAX6 mutation or not

1

-

Male

Sporadic

Sporadic

-

-

Yes

'Atypical Gillespie syndrome': ptosis, iris anomalies, foveal hypoplasia, retinal vascular tortuosity

-

+/-

02

Intron

IVS2+9G>A

c.-129+9G>A

-

-

Intronic change does not affect any known splice signals

-

PAX6_00404

-

GAGTCC

G

A

CTTCTT

-

-

Direct Sequencing

-

-

-

Case D

Microphthalmia, Nystagmus, Cataract

[17417613], United Kingdom (Great Britain):Edinburgh

DNA

Direct Sequencing

There is no evidence that this change has a functional effect on RNA processing or that it has arisen de novo in this individual. Therefore it is best considered a polymorphism at present.

1

-

-

-

Sporadic

-

No

No

Microcornea, partial sclerocornea + band shaped keratitis in left eye. Normal brain CT scan

-

-/-

02

Intron

IVS2+9G>A

c.-129+9G>A     + c.357+1G>C

-

-

Intronic change does not affect any known splice signals

-

PAX6_00541

-

GAGTCC

G

A

CTTCTT

-

-

Direct Sequencing

-

-

Normal father has same variant

Case 18

Aniridia

[18776953], United Kingdom (Great Britain):Edinburgh

DNA

SEQ

Intron 6 mutation absent from both parents. Intron 2 variant present in normal father.

1

Mexican

female

Sporadic

Sporadic

-

-

-

Subtotal aniridia, nystagmus, macular hypoplasia, ectopia lentis, microcornea, optic nerve hypoplasia

-

?/?

02

Intron

IVS2-2delA

c.-128-2delA

r.spl?

-

Probable splice error

Effect on translation unknown

PAX6_00168

1

TCTT

A

-

G/GGGGA

Deletion

-

Unknown

DdeI (-)

-

-

294-97

Aniridia

G Wildhart, unpublished, Germany:Mainz

DNA

Unknown

-

1

-

Female

-

-

Unknown

Unknown

n/a

-

-

?/?

02

Intron

IVS2-2delA

c.-128-2delA

r.spl?

-

Splice error predicted

Effect on translation unknown

PAX6_00077

1

TGTCTT

A

-

G/GGGGA

Deletion

-

Heteroduplex Analysis

DdeI (-)

-

Mutation segregates with phenotype but effect is unknown

RIBMAR

Aniridia

[9281415], United Kingdom (Great Britain):Edinburgh

DNA

Heteroduplex Analysis

Mutation destroys DdeI site

1

-

Male

Familial

Familial

Yes

Unknown

n/a

Same mutation in affected sister and niece; absent in normal brother and mother

-

?/?

02

Intron

IVS2-2delA

c.-128-2delA

r.spl?

p.?

Probable splice error

Effect on translation unknown

PAX6_00499

1

TCTT

A

-

G/GGGGA

Deletion

-

DHPLC

DdeI (-)

-

-

190

Aniridia

[18241071], United Kingdom (Great Britain):Edinburgh

DNA

DHPLC

-

1

-

-

-

Sporadic

Y

-

-

-

-

+?/?

02

Intron

IVS2-2delA

c.-128-2delA

r.spl?

-

Probable splice error

Effect on translation unknown

PAX6_00750

-

TGTCTT

A

-

G/GGGGA

Deletion

-

Direct Sequencing

-

-

-

26.03

Aniridia

[28321846], Russian Federation:Moscow

DNA

SEQ

-

1

-

male

de novo

Sporadic

-

-

-

OU: Aniridia complete, nystagmus, clear lens. rnMuscular dystonia.

-

+/+

03

Intron

IVS2-1G>T

c.-128-1G>T

r.spl?

p.?

Probable splice error

Effect unknown

PAX6_00680

1

GTCTTA

G

T

/GGGGAA

Substitution

5'UTR

Direct Sequencing

-

-

-

Patient 2 Skeens 2011

Variant Aniridia

[21376398] , United Kingdom (Great Britain):Edinburgh

DNA

SEQ

-

1

-

-

-

Familial

-

-

-

Keratopathy, limbal stem cell deficiency, abnormal corneal epithelium, iris hypoplasia

-

?/?

03

5' UTR

-

c.-118_-117delTT

-

p.?

-

-

PAX6_00931

-

-

-

-

-

Deletion

-

Direct Sequencing

-

-

-

-

congenital aniridia

Russian Federation:Moscow

DNA

SEQ

-

1

Jewish

male

de novo

Sporadic

Yes

No

-

Congenital aniridia, nystagmus, cataract, partial optic atrophy, fovea hypoplasia

-

?/?

03

Exon

c.246del4

c.-116_-112delTAAC

-

-

Effect unknown

Effect unknown

PAX6_00146

-

AGACTT

TAAC

-

TAGGGG

Deletion

-

Dideoxy Fingerprinting

-

-

Deleted sequence was originally submitted as TGAC - presumed to be a typo, since actual sequence at this position is TAAC

31 (29795)

Aniridia, Nystagmus

[10234503], Denmark:Glostrup

DNA

Dideoxy Fingerprinting

-

1

-

Male

-

-

Unknown

Unknown

n/a

Mild nystagmus; lens ectopia

-

?/?

03

Intron

IVS3+1delG

c.-52+1delG

r.spl?

-

Predicted 5'UTR splice error - outcome unknown

Outcome unknown

PAX6_00006

-

TTTCAG/

G

-

CAAGTT

Deletion

-

SSCP

-

-

-

Ch

Aniridia

[1345175], United Kingdom (Great Britain):Edinburgh

DNA

SSCP

-

1

-

Unknown

-

-

Unknown

No

n/a

Familial aniridia

-

+/+

03

Intron

IVS3+1G>A

c.-52+1G>A

r.-128_142-95del

p.?

Skipping of exons 3, 4, 5 & 5a confirmed by RT-PCR

Effect on protein unknown

PAX6_00143

1

TTTCAG/

G

A

CAAGTT

Substitution

-

Dideoxy Fingerprinting, RT-PCR

-

-

-

18 (18999)

Aniridia, Cataract, Glaucoma, Nystagmus

[10234503], Denmark:Glostrup

DNA

RT-PCR, Dideoxy Fingerprinting

-

1

-

Male

-

-

Unknown

Unknown

n/a

Familial case: mild nystagmus, early cataract, mild corneal dystrophy, glaucoma

-

+/+

03

Intron

IVS3+1G>A

c.-52+1G>A

r.spl?

p.?

Exon skipping likely by analogy with PAX6_00143

Effect on protein unknown

PAX6_00503

1

TTTCAG/

G

A

CAAGTT

Substitution

-

Direct Sequencing

-

-

-

Patient 1

Aniridia

[18483559], United Kingdom (Great Britain):Edinburgh

DNA

SEQ

-

1

-

-

-

-

-

-

-

Isolated aniridia

-

+/+

03

Intron

IVS3+1G>A

c.-52+1G>A

r.-128_142-95del

p.?

Exon skipping predicted by analogy with PAX6_00143

Effect on protein unknown

PAX6_00504

1

TTTCAG/

G

A

CAAGTT

Substitution

-

Direct Sequencing

-

-

-

Patient 53

Aniridia

[18483559], United Kingdom (Great Britain):Edinburgh

DNA

SEQ

-

1

-

-

-

-

-

-

-

Isolated aniridia

-

+/+

03

Intron

IVS3+5G>C

c.-52+5G>C

r.spl?

p.?

Splice defect predicted

Effect on protein unknown

PAX6_00505

1

AG/GCAA

G

C

TTCTGT

Substitution

-

Direct Sequencing

-

-

-

Patient 21

Aniridia

[18483559], United Kingdom (Great Britain):Edinburgh

DNA

SEQ

-

1

-

-

-

-

-

-

-

Isolated aniridia

-

+/+

3-7

Exon

-

chr11:31,778,912_31,794,631del

c.(?_-127)_523+?del

-

Deletion of exons 3-7. Abnormal splicing predicted.

-

PAX6_00780

-

-

-

-

-

Deletion

-

MLPA

-

-

vassilievat

-

Congenital aniridia

Russian Federation:Moscow

DNA

MLPA

-

1

Karachay

male

de novo

Sporadic

-

-

-

OU complete aniridia, congenital cataract, glaucoma, microcornea

Chest deformation

+/+

3-

-

-

03_13del

-

-

Deletion of exons 3-13 - effect on RNA unknown

-

PAX6_00837

-

-

-

-

-

Deletion

-

MLPA

-

-

-

Case 4 BG

Aniridia

[26849621], United Kingdom (Great Britain):Edinburgh

DNA

MLPA

-

1

-

female

-

-

-

-

-

Complete bilateral aniridia, nystagmus, cataracts

-

+/+

04

Exon

-

c.1A>C

-

p.(Met1?)

Initiation codon abolished: Met (atg) > Leu (ctg)

Possible failure of translation or initiation from cryptic start sites

PAX6_00776

1

CCAGC

A

C

TGCAG

Substitution

-

Direct Sequencing

-

-

-

A-37

Congenital aniridia

[28321846], Russian Federation:Moscow

DNA

SEQ

-

1

Russian

female

de novo

Sporadic

yes

no

yes

OU: complete aniridia, disc hypoplasia, nystagmus, microcornea

Right kidney doubling

+/+

04

Exon

c.363A>G

c.1A>G

-

p.(Met1?)

Initiation codon abolished: Met (aug) > Val (gug)

Possible failure of translation or initiation from cryptic start sites

PAX6_00167

1

GCCAGC

A

G

TGCAGA

Substitution

-

Unknown

SphI (-)

-

-

293-96

Aniridia

G Wildhart, unpublished, Germany:Mainz

DNA

Unknown

-

1

-

Male

-

Sporadic

Unknown

Unknown

Yes

-

-

+/+

04

Exon

c.363A>G

c.1A>G

-

p.(Met1?)

Initiation codon abolished: Met (aug) > Val (gug)

Possible failure of translation or initiation from cryptic start sites

PAX6_00627

1

GCCAGC

A

G

TGCAGA

Substitution

-

Direct Sequencing

SphI (-)

-

-

QT522

Aniridia

[21850189], United Kingdom (Great Britain):Edinburgh

DNA

SEQ

Mother with same mutation has coloboma-like iris defects

2

Chinese

female

Familial

Familial

-

-

-

-

Nystagmus, foveal hypoplasia, aniridia, punctate cataract

+/+

04

Exon

c.363A>G

c.1A>G

-

p.(Met1?)

Initiation codon abolished: Met (aug) > Val (gug)

Possible failure of translation or initiation from cryptic start sites

PAX6_00778

1

GCCAGC

A

G

TGCAGA

Substitution

-

Direct Sequencing

-

-

-

51AN

Congenital aniridia

[28321846], Russian Federation:Moscow

DNA

SEQ

-

1

Bulgarian

male

-

Sporadic

-

-

yes

OU: partial aniridia, cataract, nystagmus, macular and optic nerve hypoplasia, keratopathy, corpus callosum hypoplasia

asthma, pulmonary artery stenosis, maxillary sinus hypoplasia

+/+

04

Exon

c.363AT>CA

c.1_2delATinsCA

-

p.(Met1?)

Initiation codon abolished: Met (aug) > Gln (cag)

Possible failure of translation or initiation from cryptic start sites

PAX6_00125

1

GCCAGC

AT

CA

GCAGAA

Insertion/Deletion

-

SSCP

SphI (-)

-

-

SPAN18

Aniridia, Nystagmus

[9727514], United Kingdom (Great Britain):Edinburgh

DNA

SSCP

-

1

-

Female

-

Sporadic

Unknown

Unknown

n/a

Nystagmus, keratopathy, glaucoma, macular hypoplasia, abnormal ERG (rod and cone)

-

+/+

04

Exon

c.364T>A

c.2T>A

-

p.(Met1?)

Initiation codon abolished: Met (aug) > Lys (aag)

Possible failure of translation or initiation from cryptic sites

PAX6_00148

2

CCAGCA

T

A

GCAGAA

Substitution

-

Dideoxy Fingerprinting

SphI (-)

-

-

16 (19714)

Aniridia, Cataract, Glaucoma, Nystagmus

[10234503], Denmark:Glostrup

DNA

Dideoxy Fingerprinting

-

1

-

Female

-

Familial

Yes

Unknown

Yes

Intermediate nystagmus, lens ectopia, late cataract, mild corneal dystrophy, moderate photophobia, glaucoma

-

+/+

04

Exon

c.364T>A

c.2T>A

-

p.(Met1?)

Initiation codon abolished: Met (aug) > Lys (aag)

Possible failure of translation or initiation from cryptic sites

PAX6_00846

2

CCAGCA

T

A

GCAGAA

Substitution

-

Direct Sequencing

-

-

-

Proband I:1

Aniridia

[26535646], United Kingdom (Great Britain):Edinburgh

DNA

SEQ

Mutation present in 8 affected members but not in 4 unaffected members of a 3-generation family

1

Chinese

female

Familial

-

-

-

-

All affected members have aniridia, nystagmus and ptosis

-

+/+

04

Exon

c.364T>G

c.2T>G

-

p.(Met1?)

Initiation codon abolished: Met (aug) > Arg (agg)

Possible failure of translation or initation from cryptic sites

PAX6_00407

2

CCAGCA

T

G

GCAGAA

Substitution

-

DHPLC

SphI (-)

-

-

PY2K/368

Partial Aniridia

[16712695], United Kingdom (Great Britain):Edinburgh

DNA

DHPLC

-

1

-

Female

-

Familial

Yes

-

Yes

Bilateral partial aniridia. Father also affected.

-

+/+

04

Exon

c.364T>G

c.2T>G

-

p.(Met1?)

Initiation codon abolished: Met (aug) > Arg (agg)

Possible failure of translation or initation from cryptic sites

PAX6_00408

2

CCAGCA

T

G

GCAGAA

Substitution

-

DHPLC

SphI (-)

-

-

D2006/65

Aniridia

K Williamson & V van Heyningen, unpublished, United Kingdom (Great Britain):Edinburgh

DNA

DHPLC

-

1

-

Female

-

-

Yes

-

Yes

-

-

+/+

04

Exon

c.365delG

c.3delG

-

p.(Met1?)

Start codon destroyed by frame-shifting deletion

Possible failure of translation or initation from cryptic sites

PAX6_00409

3

CAGCAT

G

-

CAGAAC

Deletion

-

DHPLC

SphI (-)

-

-

D2003/85

Aniridia

[16712695], United Kingdom (Great Britain):Edinburgh

DNA

DHPLC

-

1

-

Female

Familial

Familial

Yes

-

Yes

Same mutation in similarly affected father and son

-

+/+

04

Exon

c.366delC

c.4delC

-

p.(Gln2Argfs*7)

Frameshift predicted, leading to PTC

NMD predicted - protein synthesis unlikely

PAX6_00471

4

AGCATG

C

-

AGAACA

Substitution

-

DHPLC

-

-

-

133

Aniridia

[18241071], United Kingdom (Great Britain):Edinburgh

DNA

DHPLC

-

1

-

-

-

Familial

Y

-

-

-

-

+/+

04

Exon

-

c.7_10dupAACA

-

p.(Ser4Lysfs*53)

Frame-shifting duplication leading to PTC. NMD likely

Protein synthesis unlikely

PAX6_00761

7

AGAACA

-

AACA

/GTAAGT

Duplication

PD

Direct Sequencing

-

-

Not found in 150 controls

AN-18-1

Aniridia

[25678763], United Kingdom (Great Britain):Edinburgh

DNA

SEQ

Father (AN-118-2) with same mutation has partial aniridia, nystagmus, foveal hypoplasia, cataract, glaucoma. Mutation absent from unaffected mother

1

Southern India

male

Familial

Familial

-

-

-

Aniridia, nystagmus, foveal hypoplasia, microcornea

-

+/+

04

Intron

IVS4+1G>A

c.10+1G>A

r.spl?

-

Splice error highly likely

-

PAX6_00762

10

ACAACA/

G

A

TAAGTG

Substitution

PD

Direct Sequencing

-

-

Not found in 150 controls

AN-99-1

Aniridia

[25678763], United Kingdom (Great Britain):Edinburgh

DNA

SEQ

Father (AN-99-2) with same mutation has aniridia, keratopathy, nystagmus, foveal hypoplasia, cataract, glaucoma. Mutation absent from unaffected mother

1

Southern India

male

Familial

Familial

-

-

-

Aniridia, nystagmus, foveal hypoplasia

-

+/+

04

Intron

IVS4+3AA>GC

c.10+3_+4delAAinsGC

r.-51_10del

p.?

Skipping of exon 4 confirmed by RT-PCR

Possible failure of translation or initiation from cryptic start sites

PAX6_00051

10

AACA/GT

AA

GC

GTG

Insertion/Deletion

-

SSCP, RT-PCR, Chemical Cleavage of Mismatch

-

-

-

p236113

Aniridia

[9138149], United Kingdom (Great Britain):Edinburgh

DNA

RT-PCR, SSCP, Chemical Cleavage of Mismatch

-

1

-

Female

-

Familial

Yes

No

Splice donor

-

-

+/+

04

Intron

IVS4+5G>C

c.10+5G>C

r.-51_10del

p.?

Skipping of exon 4 confirmed by RT-PCR

Possible failure of translation or initiation from cryptic start sites

PAX6_00383

10

CA/GTAA

G

C

TGCCTC

-

PD

SSCP, RT-PCR

-

-

-

1

Nystagmus, Iris Hypoplasia, Foveal Hypoplasia

[15629294], United Kingdom (Great Britain):Edinburgh

DNA

RT-PCR, SSCP

Authors suggest possible use of alternative initiation codon in exon 3. Erroneously entered in old database as IVS+4G>C

1

-

Female

Familial

Familial

-

No

-

Affected mother and two maternal aunts have variable iris defects with foveal hypoplasia and nystagmus

-

+/+

04

Intron

IVS4+5G>C

c.10+5G>C

r.spl?

p.?

Probable splice error

Skipping of exon 4 likely by analogy with PAX6_00383

PAX6_00298

10

CA/GTAA

G

C

TGCCTC

-

-

SSCP, DGGE

-

-

-

00/1087

Iris Hypoplasia, Nystagmus, Foveal Hypoplasia

[12634864], United Kingdom (Great Britain):Edinburgh

DNA

DGGE, SSCP

-

1

-

Unknown

-

Familial

Unknown

No

-

Atypical coloboma

-

-/-

04

Intron

IVS4-85T>C

c.11-85T>C

-

p.(=)

No effect predicted

No effect predicted

PAX6_00575

11

TCATCT

T

C

CCTCTT

Substitution

PD

Direct Sequencing

-

1/570

-

Maekawa et al

Autism

[19607881], United Kingdom (Great Britain):Edinburgh

DNA

SEQ

-

1

285 autistic Japanese subjects

-

-

-

-

-

-

-

-

-/-

04

Intron

IVS4-70_72delTCT

c.11-70_72delTCT

-

p.(=)

No effect predicted

No effect predicted

PAX6_00577

11

CCTTCT

TCT

-

CCCTCT

Deletion

PD

Direct Sequencing

-

1/570

-

Maekawa et al

Autism

[19607881], United Kingdom (Great Britain):Edinburgh

DNA

SEQ

-

1

285 autistic Japanese subjects

-

-

-

-

-

-

-

-

-/-

04

Intron

IVS4-42C>T

c.11-42C>T

-

p.(=)

No effect prediced

No effect predicted

PAX6_00576

11

TGCTCT

C

T

TTCTCT

Substitution

PD

Direct Sequencing

-

1/570

-

Maekawa et al

Autism

[19607881], United Kingdom (Great Britain):Edinburgh

DNA

SEQ

-

1

285 autistic Japanese subjects

-

-

-

-

-

-

-

-

-/-

04

Intron

IVS4-41T>C

c.11-41T>C

-

p.(=)

Substitution at intronic position -41 predicted; unlikely to affect splicing

No change expected

PAX6_00410

11

GCTCTC

T

C

TCTCCT

-

-

DHPLC

-

-

-

D2001/78

Peters anomaly

K Williamson & V van Heyningen, unpublished, United Kingdom (Great Britain):Edinburgh

DNA

DHPLC

Substitution at position -41 of intron 4 is probably a neutral polymorphism

1

-

-

-

-

Yes

-

No

Bilateral Peters anomaly

Tetralogy of Fallot; Hirschprung Disease

+/+

04

Intron

IVS4-2A>G

c.11-2A>G

r.spl?

p.?

Splice error predicted

Protein outcome unclear without RNA analysis

PAX6_00067

11

TTCCTC

A

G

G/GTCAC

Substitution

PD

SSCP

AvaI (+)

-

-

DEDOW

Aniridia

[10857836], United Kingdom (Great Britain):Edinburgh

DNA

SSCP

-

1

-

Male

-

Familial

Yes

Unknown

n/a

-

-

+/+

04

Intron

IVS4-2A>G

c.11-2A>G

r.spl?

p.?

Splice defect highly likely

Effect on protein unknown

PAX6_00637

11

TTCCTC

A

G

GGTCAC

Substitution

PD

Direct Sequencing

-

-

-

Case 1-2

Aniridia

[22393275], United Kingdom (Great Britain):Edinburgh

DNA

SEQ

Mother with same mutation has aniridia, nystagmus, cataract and macular hypoplasia

2

Korean

female

Familial

Familial

-

-

-

Aniridia, nystagmus, keratopathy, corneal opacity

-

+/+

04

Intron

IVS4-2A>G

c.11-2A>G

r.spl?

p.?

Splice error predicted

Protein outcome unclear without RNA analysis

PAX6_00671

11

TTCCTC

A

G

G/GTCAC

Substitution

PD

Direct Sequencing

-

-

Variant absent from 100 controls

P2

Aniridia

[21904390], United Kingdom (Great Britain):Edinburgh

DNA

SEQ

-

1

Chinese

-

-

Sporadic

-

-

-

Bilateral complete aniridia, congenital cataract, nystagmus

-

+/+

05

Exon

-

chr11:31,760,458-31,823,847

-

-

Deletion of exons 5a to 13. Effect on RNA unknown

-

PAX6_00887

-

-

-

-

-

Deletion

-

CGH

-

-

Deletion of 63 Kb of exons 5a to 13 of PAX6 and ELP4, also detected by MLPA in the affected mother

Blanco-Kelly 2017

Aniridia

Blanco-Kelly et al 2017 [28231309], Spain:Madrid

DNA

CGH

Deletion of 63 Kb of exons 5a to 13 of PAX6 and ELP4, also detected by MLPA in the affected mother

1

Spanish

male

Maternal

Familial

-

-

-

Isolated aniridia

-

+?/?

05

Exon

-

c.19G>C

-

p.(Gly7Arg)

-

-

PAX6_00732

19

CACAGC

G

C

GAGTGA

Substitution

-

Direct Sequencing

-

-

vassilievat

11.21

Aniridia

[28321846], Russian Federation:Moscow

DNA

SEQ

Mother with same mutation has partial aniridia

1

-

female

-

Familial

-

-

-

Aniridia complete, nystagmus, keratopathy grade I, lens subluxation

Residual encephalopathy, mild hypotonic syndrome, talipes valgus, right palm chondroma

+/+

05

Exon

c.381G>T

c.19G>T

-

p.(Gly7*)

Gly (gga) >Ter (tga) predicted

NMD predicted - protein synthesis unlikely

PAX6_00472

19

CACAGC

G

T

GAGTGA

Substitution

PD

DHPLC

-

-

-

130

Aniridia

[18241071] , United Kingdom (Great Britain):Edinburgh

DNA

DHPLC

-

1

-

-

-

Sporadic

Y

-

-

-

-

+/+

05

Exon

c.381G>T

c.19G>T

-

p.(Gly7*)

Gly (gga) >Ter (tga) predicted

NMD predicted - protein synthesis unlikely

PAX6_00638

19

CACAGC

G

T

GAGTGA

Substitution

PD

Direct Sequencing

-

-

-

Case 2

Aniridia

[22393275], United Kingdom (Great Britain):Edinburgh

DNA

SEQ

-

1

Korean

male

-

Sporadic

-

-

-

Aniridia, nystagmus, keratopathy, cataract

-

+/+

05

Exon

c.388A>T

c.26A>T

-

p.(Asn9Ile)

Asn (aau) > Ile (auu) predicted

Predicted missense mutation. Asn9 is conserved in all paired domains

PAX6_00411

26

GAGTGA

A

T

TCAGCT

Substitution

PD

DHPLC

-

-

-

D2002/53

Nystagmus, Ectopia Pupillae

[16712695], United Kingdom (Great Britain):Edinburgh

DNA

DHPLC

In the genomic sequence trace (from blood DNA) the mutant allele was present at approximately 10%. Therefore this individual may be a somatic mosaic for the mutation

1

-

Female

-

-

Yes

-

Yes

Variant aniridia: nystagmus with nasally displaced pupils

-

+/+

05

Exon

c.389_393dupTCAGC

c.27_31dupTCAGC

-

p.(Gly12Serfs*21)

PTC predicted - NMD likely

Protein synthesis unlikely

PAX6_00398

27

ATCAGC

-

TCAGC

TCGGTG

Duplication

PD

SSCP

-

-

-

ANF8-1

Aniridia, Cataract, Foveal Hypoplasia, Nystagmus

[16803629], United Kingdom (Great Britain):Edinburgh

DNA

SSCP

-

1

-

Male

Familial

Familial

-

-

n/a

Bilateral keratopathy. Affected relatives have same mutation

-

?/?

05

Exon

c.390C>T

c.28C>T

-

p.(Gln10*)

Early nonsense mutation - NMD of RNA predicted

Protein synthesis unlikely - NMD of RNA predicted

PAX6_00412

28

GTGAAT

C

T

AGCTCG

Substitution

PD

DHPLC

-

-

-

PY2K/356

Aniridia

[16712695], United Kingdom (Great Britain):Edinburgh

DNA

DHPLC

-

1

-

Female

-

-

Yes

-

n/a

Possible familial mutation - half brother has bilateral iris anomaly and cataracts. Common father is normal - possible gonadal mosaic

-

+/+

05

Exon

c.390C>T

c.28C>T

-

p.(Gln10*)

Early nonsense mutation - NMD of RNA predicted

Protein synthesis unlikely - NMD of RNA predicted

PAX6_00781

28

GTGAAT

C

T

AGCTCG

Substitution

PD

Direct Sequencing

-

-

-

157

Anridia

[26661695], United Kingdom (Great Britain):Edinburgh

DNA

SEQ

-

1

-

female

-

Sporadic

-

-

-

Classical aniridia

-

?/?

05

Exon

c.395delC

c.33delC

-

p.(Gly12Valfs*19)

PTC predicted - NMD likely

Protein synthesis unlikely

PAX6_00100

33

TCAGCT

C

-

GGTGGT

Deletion

PD

SSCP

-

-

-

187HD

Aniridia

[9792406], Germany:Mainz

DNA

SSCP

-

1

-

Female

-

Familial

Unknown

No

n/a

-

-

+/+

05

Exon

c.396G>C

c.34G>C

-

p.(Gly12Arg)

Gly (ggt) > Arg (cgt) predicted

Missense change predicted

PAX6_00509

34

CAGCTC

G

C

GTGGTG

Substitution

PD

Direct Sequencing

-

-

-

Patient 19

Aniridia

[18483559], United Kingdom (Great Britain):Edinburgh

DNA

SEQ

-

1

-

-

-

-

-

-

-

Isolated aniridia

-

?/?

05

Exon

c.402del2

c.40_41delGT

-

p.(Val14Leufs*41)

PTC predicted - NMD likely

Protein synthesis unlikely

PAX6_00355

40

GGTGGT

GT

-

CTTTGT

Deletion

PD

Direct Sequencing

-

-

-

c.402del2

Aniridia, Diabetes mellitus

Nishi M et al 2004 Diabetic Medicine 22 641-644, Japan:Wakayama

DNA

Direct Sequencing

-

1

-

Female

-

Sporadic

Unknown

Unknown

Unknown

Aniridia, strabismus. Normal olfaction, normal brain MRI scan

Early-onset diabetes mellitus; may be associated with PAX6 mutation since PAX6 is expressed in the endocrine pancreas

+/+

05

Exon

c.406_407delTT

c.44_45delTT

-

p.(Phe15Argfs*40)

PTC predicted - NMD of RNA likely

Protein synthesis unlikely

PAX6_00397

44

GTGTCT

TT

-

GTCAAC

Deletion

PD

SSCP

-

-

-

ANF9-1

Aniridia, Foveal Hypoplasia, Nystagmus

[16803629], United Kingdom (Great Britain):Edinburgh

DNA

SSCP

-

1

-

Female

-

Familial

-

-

n/a

Father also affected

-

?/?

05

Exon

c.412A>G

c.50A>G     + c.85A>G, c.141+14_+25dup12

-

p.(Asn17Ser)

Asn (aac) > Ser (agc) predicted

Predicted missense mutation

PAX6_00192

50

TTGTCA

A

G

CGGGCG

Substitution

PD

SSCP

-

-

Patient has 2 other PAX6 variants, c.85A>G and c.141+14_+25dup12

Patient 1

Foveal Hypoplasia, Aniridia, Cataract, Nystagmus

[9856761], United Kingdom (Great Britain):Edinburgh

DNA

SSCP

Patient has 3 changes c.50A>G, c.85A>G and c.141+14_+25dup12 on the same allele. Unknown if any of these has occurred de novo. Substitution of I29 has previously been noted (p.Ile29Ser) so c.85A>G may be the pathological mutation

1

-

Female

-

Sporadic

Unknown

Yes

Yes

Nystagmus, cataract, foveal hypoplasia.

-

+?/+?

05

Exon

c.412A>G

c.50A>G

-

p.(Asn17Ser)

Asn (aac) > Ser (agc) predicted

Predicted missense mutation

PAX6_00849

50

TTGTCA

A

G

CGGGCG

Substitution

PD

Direct Sequencing

-

-

-

Patient 1

Aniridia

[27081561], United Kingdom (Great Britain):Edinburgh

DNA

SEQ

-

1

-

female

-

Sporadic

-

-

-

Total aniridia, bilateral cataract, foveal hypoplasia

-

+/+

05

Exon

-

c.50dupA

-

p.(Asn17Lysfs*39)

Frame-shifting insertion leading to PTC. NMD predicted.

Protein synthesis unlikely

PAX6_00920

50

TCTCAA

-

A

CGGGCG

Duplication

PD

Direct Sequencing

-

-

-

Family 1 III-2

Aniridia

[28157223], United Kingdom (Great Britain):Edinburgh

DNA

SEQ

-

1

-

female

-

Familial

-

-

-

Aniridia, cataract, nystagmus, corneal opacity, microphthalmia

-

+/+

05

Exon

c.413C>A

c.51C>A

-

p.(Asn17Lys)

Asn (aac) > Lys (aaa) predicted

Paired domain missense mutation predicted

PAX6_00600

51

TGTCAA

C

A

GGGCGG

Substitution

PD

Direct Sequencing

-

0/200

-

Jia et al

Peters anomaly

[20405024], United Kingdom (Great Britain):Edinburgh

DNA

SEQ

-

1

Chinese

-

-

-

-

-

Yes

Bilateral Peters anomaly, congenital nystagmus, corneal leukoma with anterior synechia, anterior polar cataract, retinal hypoplasia, microphthalmia

-

+/+

05

Exon

c.414G>A

c.52G>A

-

p.(Gly18Arg)

Gly (ggg) > Arg (agg) predicted

Predicted missense mutation

PAX6_00308

52

GTCAAC

G

A

GGCGGC

Substitution

PD

DHPLC

-

-

-

GRAAL

Peters anomaly

[12015275], United Kingdom (Great Britain):Edinburgh

DNA

DHPLC

-

1

-

Male

-

Familial

Yes

No

Yes

Patient has bilateral Peters anomaly; father has Axenfeld-Rieger anomaly

-

+/+

05

Exon

c.414G>T

c.52G>T

-

p.(Gly18Trp)

Gly (ggg) > Trp (ugg) predicted

Predicted missense mutation

PAX6_00117

52

GTCAAC

G

T

GGCGGC

Substitution

PD

SSCP

-

-

-

205HD

Congenital cataract

[9792406], Germany:Mainz

DNA

SSCP

-

1

-

Female

Familial

Familial

Unknown

No

n/a

Secondary glaucoma. Mother with Peters anomaly has same mutation

-

+/+

05

Exon

c.418G>C

c.56G>C

-

p.(Arg19Pro)

Arg (cgg) > Pro (ccg) predicted

Predicted missense mutation

PAX6_00289

56

AACGGG

G

C

GCCACT

Substitution

PD

SSCP, DGGE

-

-

-

98/217

Partial Aniridia, Microphthalmia, Cataract

[12634864] [24033328], United Kingdom (Great Britain):Edinburgh

DNA

DGGE, SSCP

-

1

-

Unknown

-

Familial

Unknown

No

Yes

Sclerocornea

-

+/+

05

Exon

-

c.57delG

-

p.(Pro20Hisfs*11)

Frame-shifting deletion leading to PTC

NMD predicted - protein synthesis unlikely

PAX6_00782

57

CGGGCG

G

-

CCACTG

Deletion

PD

Direct Sequencing

-

-

-

118

Aniridia

[26661695], United Kingdom (Great Britain):Edinburgh

DNA

SEQ

-

1

-

male

-

Sporadic

-

-

-

Classical aniridia

-

+/+

05

Exon

-

c.63-70delGCCGGACT

-

p.Pro22Hisfs*31

Frame-shifting deletion leading to PTC

NMD predicted - protein synthesis unlikely

PAX6_00783

63

GCCACT

GCCGGACT

-

CCACCC

Deletion

PD

Direct Sequencing

-

-

-

108

Aniridia

[26661695], United Kingdom (Great Britain):Edinburgh

DNA

SEQ

-

1

-

male

-

Familial

-

-

-

Classical aniridia

-

+/+

05

Exon

c.427insT

c.65_66insT

-

p.(Asp23Glyfs*33)

PTC predicted - NMD likely

Protein synthesis unlikely

PAX6_00171

65

ACTGCC

-

T

GGACTC

Insertion

PD

Unknown

-

-

-

367-97

Aniridia

G Wildhart, unpublished, Germany:Mainz

DNA

Unknown

-

1

-

Female

-

Familial

Unknown

Unknown

n/a

-

-

+/+

05

Exon

c.427del15

c.65_79del15

-

p.(21_25del5)

Predicted in-frame deletion

Predicted deletion of 5 aa (PDSTR) from the first alpha helix of the N-terminal paired subdomain

PAX6_00074

65

CACTGC

CGGACTCCACCCGGC

-

AGAAGA

Deletion

PD

SSCP, DGGE

-

-

-

E5del15

Aniridia

[12634864], United Kingdom (Great Britain):Edinburgh

DNA

DGGE, SSCP

This is patient 95/06 in Eur J Hum Genet 11 163-169. The mutation was confirmed independently - see Mol Cell Probes 11 287-292, patient LASER)

1

-

Female

-

Familial

Yes

Unknown

n/a

-

-

+/+

05

Exon

c.432delT

c.70delT

-

p.(Ser24Profs*7)

PTC predicted - NMD likely

Protein synthesis unlikely

PAX6_00030

70

CCGGAC

T

-

CCACCC

Deletion

PD

Unknown

-

-

-

Bo

Aniridia

Glaser T et al (1995) Mol Genetics of Ocular Disease pp51-82, United Kingdom (Great Britain):Edinburgh

DNA

Unknown

-

1

-

Male

-

-

Unknown

Unknown

n/a

Son has typical aniridia; father has comparatively normal eyes - not diagnosed until age 51

-

+/+

05

Exon

c.434delC

c.72delC

-

p.(Thr25Profs*6)

PTC predicted - NMD likely

Protein synthesis unlikely

PAX6_00414

72

GGATCT

C

-

ACCCGG

Deletion

PD

DHPLC

-

-

-

PY2K/372 PARTE

Aniridia, Rieger anomaly

K Williamson & V van Heyningen, unpublished, United Kingdom (Great Britain):Edinburgh

DNA

DHPLC

-

1

-

Female

-

-

-

-

-

Unusual bilateral iris colobomas, aniridia, Rieger anomaly

-

+/+

05

Exon

c.434ins11

c.72_73ins11

-

p.(Thr25Cysfs*10)

Predicted frameshift leading to PTC - NMD likely

Protein synthesis unlikely

PAX6_00018

72

GACTCC

-

TGCGGACCTCC

ACCCGG

Insertion

PD

SSCP

-

-

Insertion appears to be a duplication with an extra base added

VMR1

Aniridia

[7909985], United Kingdom (Great Britain):Edinburgh

DNA

SSCP

Passed from females 7x and from males 6x in large pedigree

1

-

Female

-

Familial

Unknown

Unknown

n/a

-

-

+/+

05

Exon

c.438C>G

c.76C>G

-

p.(Arg26Gly)

Arg (cgg) > Gly (ggg) predicted

Arg26Gly protein has reduced DNA binding activity (Hum Mol Gen 6, 381, 1997)

PAX6_00035

76

TCCACC

C

G

GGCAGA

Substitution

PD

Direct Sequencing

-

-

Substitution of arginine by glycine near N-terminal end of first alpha-helix; important for DNA binding

SOBHA (II-3)

Peters anomaly

[8162071], United Kingdom (Great Britain):Edinburgh

DNA

Direct Sequencing

Patient has Peters anomaly, iris hypoplasia, posterior embryotoxon and glaucoma. Mother (I-2) and sister (II-2) with same mutation have iris hypoplasia and posterior embryotoxon

1

-

Male

Familial

Familial

Yes

No

Yes

-

-

+/+

05

Exon

c.439G>C

c.77G>C

-

p.(Arg26Pro)

Arg (CGG) > Pro (CCG) predicted

Missense change predicted

PAX6_00510

77

CCACCC

G

C

GCAGAA

Substitution

PD

Direct Sequencing

-

-

-

Patient 44

Variant aniridia

[18483559], United Kingdom (Great Britain):Edinburgh

DNA

SEQ

-

1

-

-

-

Familial

-

-

-

Daughter has ectopic pupils, iris atrophy, nystagmus and cataract. Mother has nystagmus, microcornea, iris coloboma, stromal atrophy, peripheral choroidal coloboma

-

+/?

05

Exon

-

c.78delG

-

p.(Gln27Argfs*4)

-

-

PAX6_00727

78

CACCCG

G

-

CAGAAG

Deletion

-

Direct Sequencing

-

-

vassilievat

63AN

Congenital aniridia

[28321846], Russian Federation:Moscow

DNA

SEQ

-

1

Russian

male

de novo

Sporadic

yes

no

-

OU: complete aniridia, nystagmus, compensated glaucoma, cataract, keratopathy

-

+/+

05

Exon

-

c.79C>T     + c.357+1G>A

-

p.(Gln27*)

Gln (cag) > Ter (uag) predicted

NMD predicted - protein synthesis unlikely

PAX6_00851

79

ACCCGG

C

T

AGAAGA

Substitution

PD

Direct Sequencing

-

-

-

Patient 3

-

[27081561], United Kingdom (Great Britain):Edinburgh

DNA

SEQ

Patient has two de novo mutations. Based on the phenotype, they are probably on the same allele, but this has not been confirmed.

1

-

male

-

Sporadic

-

-

-

Total aniridia, bilateral cataract, foveal hypoplasia

-

+/+

05

Exon

c.442delA

c.80delA

-

p.(Gln27Argfs*4)

PTC predicted - NMD likely

Protein synthesis unlikely

PAX6_00227

80

CCCGGC

A

-

GAAGAT

Deletion

PD

SSCP, Heteroduplex Analysis

-

-

-

-

Aniridia

[10737978], United States:

DNA

SSCP, Heteroduplex Analysis

P1 in Hum Mut 15 332-339

1

-

-

-

Familial

Yes

Unknown

Unknown

-

-

+/+

05

Exon

c.472ins31

c.80_110dup31

-

p.(Arg38Glufs*28)

Predicted frameshift leading to PTC - NMD likely

Protein synthesis unlikely

PAX6_00303

80

CGGGGC

-

+31

CCGGCC

Duplication

PD

SSCP, DGGE

-

-

Mutation is a precise duplication of bases 80-110 (ie an insertion of 31 bases)

-

Aniridia

[12634864], United Kingdom (Great Britain):Edinburgh

DNA

DGGE, SSCP

-

1

-

-

-

-

Unknown

No

n/a

-

-

+/+

05

Exon

-

c.83_85delAGA

-

p.(Lys28del)

In-frame deletion of one codon predicted

Deletion of lysine from first helix of PD

PAX6_00663

83

GGCAGA

AGA

-

TTGTAG

Deletion

PD

Direct Sequencing

-

-

-

71158

Microcornea

Wang 2012 [22893676], United Kingdom (Great Britain):Edinburgh

DNA

SEQ

Affected father not tested

1

35 Chinese microcornea cases

female

-

Familial

-

-

-

Bilateral microcornea (8 mm), ptosis, partial iris hypoplasia, mild optic nerve hypoplasia, foveal hypoplasia

-

+/+

05

Exon

-

c.83_85delAGA

-

p.(Lys28del)

In-frame deletion of one codon predicted

Deletion of lysine from first helix of PD

PAX6_00664

83

GGCAGA

AGA

-

TTGTAG

Deletion

PD

Direct Sequencing

-

-

-

71987 (III:2)

Microcornea

Wang 2012 [22893676], United Kingdom (Great Britain):Edinburgh

DNA

SEQ

Affected dizygotic twin III:2 has same mutation. Affected father not tested.

1

35 Chinese microcornea patients

male

-

Familial

-

-

-

Bilateral microcornea (9 mm), full iris with mild structural anomaly, foveal hypoplasia

-

?/?

05

Exon

-

c.83_89delinsGA

-

p.(Lys28Argfs*26)

-

-

PAX6_00933

-

CCACTGCCGGACTCCACCCGGCAGA

AGATTGT

GA

AGAGCTAGCTCACAGCGGGGCCCGG

Insertion/Deletion

-

Direct Sequencing

-

-

-

-

congenital aniridia

Russian Federation:Moscow

DNA

SEQ

-

1

-

male

-

-

Yes

No

-

Congenital aniiridia, nystagmus, cataract, keratopathy, optic disc and fovea hypoplasia, epicanthus, ptosis

-

+/+

05

Exon

c.447A>G

c.85A>G     + c.50A>G, c.141+14_+25dup12

-

p.(Ile29Val)

Ile (auu) > Val (guu) predicted

Missense substitution of invariant isolecuine

PAX6_00193

85

CAGAAG

A

G

TTGTAG

Substitution

PD

SSCP

-

-

-

Patient 1

Foveal Hypoplasia, Aniridia, Cataract, Nystagmus

[9856761], United Kingdom (Great Britain):Edinburgh

DNA

SSCP

Patient has 3 changes c.50A>G, c.85A>G and c.141+14_+25dup12 on the same allele. Unknown if any of these has occurred de novo. Substitution of I29 has previously been noted (p.Ile29Ser) so c.85A>G may be the pathological mutation

1

-

Female

-

Sporadic

Unknown

Yes

Yes

Nystagmus, cataract, foveal hypoplasia.

-

+/+

05

Exon

c.448T>G

c.86T>G

-

p.(Ile29Ser)

Ile (auu) > Ser (agu) predicted

Substitution of invariant isoleucine predicted

PAX6_00172

86

AGAAGA

T

G

TTGTAG

Substitution

PD

Unknown

-

-

-

372-97

Aniridia

G Wildhart, unpublished, Germany:Mainz

DNA

Unknown

Isoleucine is conserved at this position (in the first alpha helix of the N-terminal subdomain) in all paired domains sequenced to date.

1

-

Female

-

Sporadic

Unknown

Unknown

Yes

-

-

+/+

05

Exon

-

c.87_90dupTGTA

-

p.(Glu31Cysfs*26)

Frame-shifting insertion predicted to introduce PTC

NMD predicted - protein synthesis unlikely

PAX6_00639

87

ATTGTA

-

TGTA

GAGCTA

Duplication

PD

Direct Sequencing

-

-

-

Case 3

Aniridia

[22393275], United Kingdom (Great Britain):Edinburgh

DNA

SEQ

-

1

Korean

male

-

Sporadic

-

-

-

Aniridia, nystagmus, cataract

-

+/+

05

Exon

c.456C>G

c.94C>G

r.(spl)?

p.(Leu32Val)/p.?

Leu (cua) > Val (gua) predicted. Possible creation of splice donor predicted by in silico analysis

Predicted missense change or splice mutation (outcome unknown)

PAX6_00473

94

GTAGAG

C

G

TAGCTC

Substitution

PD

DHPLC

-

-

-

166

Aniridia

[18241071] , United Kingdom (Great Britain):Edinburgh

DNA

DHPLC

-

1

-

-

-

Familial

Y

-

-

-

-

+/+

5

Exon

c.457_467dupTAGCTCACAGC

c.95_105dup11

-

p.(Gly36*)

Duplication of 11 bases predicted

Protein synthesis unlikely

PAX6_00668

95

GTAGAGC

-

-

GGGGCCC

Duplication

PD

Direct Sequencing

-

-

de novo mutation

II:1

Aniridia

[24787241], China:Fuzhou

DNA

SEQ

Same mutation present in the affected son of the proband but not in the proband's unaffected parents.

1

China

male

-

Familial

-

-

-

Foveal hypoplasia, nystagmus and presenile cataracts

-

+/+

05

Exon

c.459G>C

c.97G>C

-

p.(Ala33Pro)

Ala (gcu) > Pro (ccu) predicted

Missense mutation predicted

PAX6_00159

97

GAGCTA

G

C

CTCACA

Substitution

PD

SSCP

-

-

Introduction of proline predicted to disrupt first alpha-helix of paired domain

SACUP

Congenital cataract, Partial aniridia

[9931324], United Kingdom (Great Britain):Edinburgh

DNA

SSCP

-

1

-

Female

Familial

Familial

Yes

Unknown

Yes

Partial aniridia with significant iris remnants; congenital cataracts. Father (BACUP) similarly affected

-

?/?

05

Exon

-

c.100dup

-

p.(His34Profs*22)

-

-

PAX6_00937

-

CGGCAGAAGATTGTAGAGCTAGCTC

-

C

ACAGCGGGGCCCGGCCGTGCGACAT

Duplication

PD

Direct Sequencing

-

-

-

-

congenital aniridia

Russian Federation:Moscow

DNA

SEQ

-

1

-

male

-

-

Yes

No

-

Congenital aniridia, nystagmus, cataract, keratopathy, optic nerve disc and fovea hypoplasia

Hyposthenic back posture

+/+

05

Exon

-

c.101dupA

-

p.(His34Glnfs*22)

Frame-shifting insertion predicted to create PTC

NMD predicted; protein synthesis unlikely

PAX6_00623

101

AGCTCA

-

A

CAGCGG

Duplication

PD

Direct Sequencing

-

-

-

QT464

Aniridia

[21850189], United Kingdom (Great Britain):Edinburgh

DNA

SEQ

Mother and maternal grandfather also affected

1

Chinese

male

-

Familial

-

-

-

Nystagmus, foveal hypoplasia, aniridia, punctate cataract

-

+/+

05

Exon

c.429_439del11

c.103_113del11

-

p.(Asp23Alafs*29)

PTC predicted - NMD likely

Protein synthesis unlikely

PAX6_00413

103

CTGCCG

GACTCCACCCG

-

GCAGAA

Deletion

PD

DHPLC

-

-

-

PY2K/515

Aniridia

[16712695], United Kingdom (Great Britain):Edinburgh

DNA

DHPLC

-

1

-

Male

-

Sporadic

Yes

-

n/a

-

-

+/+

05

Exon

c.468G>A

c.106G>A

-

p.(Gly36Arg)

Gly (ggg) > Arg (agg) predicted

Missense substitution of invariant glycine predicted

PAX6_00364

106

CACAGC

G

A

GGGCCC

Substitution

PD

DHPLC

-

-

-

PY2K/457 2/1B

Cataract, Iris anomaly

Hingorani 2009 2/1B [19218613], United Kingdom (Great Britain):Edinburgh

DNA

DHPLC

Patient 2/1B in Hingorani 2009; mother is patient 2/1A

1

-

Female

Familial

Familial

Yes

No

Yes

Iris anomaly and early cataracts. Same mutation in similarly affected mother

-

+/+

05

Exon

c.468G>T

c.106G>T

-

p.(Gly36Trp)

Gly (ggg) > Trp (ugg) predicted

Predicted substitution of invariant glycine in paired domain

PAX6_00415

106

CACAGC

G

T

GGGCCC

Substitution

PD

DHPLC

-

-

-

PY2K/015 AMBRI

Aniridia, Glaucoma

[16712695], United Kingdom (Great Britain):Edinburgh

DNA

DHPLC

Alternate patient ID is MEP3-10

1

-

Female

-

Familial

Yes

-

Yes

Glaucoma secondary to bilateral aniridia. Probable familial case - deceased father had nystagmus and unilateral retinal detachment

-

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Legend: [ PAX6 full legend ]
Sequence variations are described basically as recommended by the Ad-Hoc Committee for Mutation Nomenclature (AHCMN), with the recently suggested additions (den Dunnen JT and Antonarakis SE [2000], Hum.Mut. 15:7-12); for a summary see Nomenclature. Coding DNA Reference Sequence, with the first base of the Met-codon counted as position 1.
Path.: Variant pathogenicity, in the format Reported/Concluded; '+' indicating the variant is pathogenic, '+?' probably pathogenic, '-' no known pathogenicity, '-?' probably no pathogenicity, '?' effect unknown. Exon: Exon numbering. Each number covers the exon and the following intron. Exon 5a is classified as part of exon 05. Location: Location of the genomic change. Legacy DNA ID: Legacy mutation nomenclature using the original PAX6 cDNA numbering. DNA change: Variation at DNA level (see full legend for details and examples). RNA change: Variation at RNA level (see full legend for details and examples). Protein change: Variation at protein level (see full legend for details and examples). RNA information: Additional information about RNA change. Protein information: Additional information about protein change. PAX6 DB-ID: DataBase IDentifier; unique identifier for each mutation. Base number: Position of change within cDNA. 5' Sequence Context: Bases immediately 5' of the sequence change. Original Sequence: The original (wild type) sequence. Variant Sequence: The new (mutant or variant) sequence. 3' Sequence Context: Bases immediately 3' of the sequence change. Type: Type of variant at DNA level. Domain: PAX6 protein domain. Detection Method: Technique used to detect the mutation. RE Site: Variant creates (+) or destroys (-) a restriction enzyme recognition site. Frequency: Frequency of polymorphism or variant. Remarks: Other information. Patient ID: Internal patient reference Disease: Disease phenotype, as reported in paper/by submitter, unless modified by the curator. Reference/Submitter: Links to PubMed ID (if available) and Submitter ID Template: Variant detected in DNA, RNA and/or Protein. Technique: Technique used to detect the variation. # Reported: Number of times this case has been reported Population: Patient population Gender: Patient gender Sequence Inheritance: Sequence Inheritance Phenotype Inheritance: Phenotype Inheritance Second PCR: Second PCR CIS: Other Mutation in Cis Conserved residue: Variation affects conserved base or amino acid Related Phenotype: Related Phenotype Unrelated Phenotype: Unrelated Phenotype