 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
+/+ |
- |
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 |
- |