PAX6 Mutations and Clinical Features of Congenital Aniridia

Ho Kim Jong; Sung Hwang Bo; Ho Lee Jung; Cheol Cha Soon

doi:10.3341/jkos.2008.49.11.1794

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Jong, Bo, Jung, and Soon: PAX6 Mutations and Clinical Features of Congenital Aniridia

Original Article

J Korean Ophthalmol Soc 2008;49(11):1794-1800.

Published online: 7 September 2008

DOI: https://doi.org/10.3341/jkos.2008.49.11.1794

PAX6 Mutations and Clinical Features of Congenital Aniridia

Ho Kim Jong, M.D., Ph.D.¹, Sung Hwang Bo, M.D.¹, Ho Lee Jung, M.D.², Cheol Cha Soon, M.D., Ph.D.^1,

¹Department of Ophthalmology, Yeungnam University College of Medicine, Daegu, Korea

²Cheil Eye Hospital, Daegu, Korea

Address reprint requests to Soon Cheol Cha, M.D., Ph.D. Department of Ophthalmology, Yeungnam University College of Medicine #317-1 Daemyung-dong, Nam-gu, Daegu 705-717, Korea Tel: 82-53-620-3442, Fax: 82-53-626-5936, E-mail: sccha@med.yu.ac.kr

Received 21 July 2008 Accepted 2 June 2008

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Purpose

To report the PAX6 mutations and clinical features in Korean aniridia patients.

Methods

Genomic DNA was isolated from 12 aniridia patients and 5 normal controls. The coding regions of the PAX6 gene were analyzed by direct sequencing of polymerase chain reaction products. The relationship between the mutational types and the ophthalmic findings from medical records was determined.

Results

Mutation analysis demonstrated seven different types of mutations, five of which have not previously been reported. Notably, these mutations were confined to PD and LNK in the PAX6 gene. Although R44X and W156X were recurrent mutations, novel mutations included G18R, IVS6+1insG, A139P, A139A, and G141G. Glaucoma was found in five (42%, adult patients 30 years or older) of twelve patients, of whom four were male.

Conclusions

This is the first report to identify the PAX6 gene mutations in Korean aniridia patients. Our limited data show that glaucoma was more prevalent in male and adult patients. Moreover, a patient’s age along with the PAX6 genotype might be a factor related to glaucoma in aniridia patients.

Keywords: Aniridia, Glaucoma, Mutation, PAX6 gene

References

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Figure 1.

Mutations of the PAX6 gene in patients. (A) A single guanine residue transversion to cytosine (c.414G>C (G18R) in exon 5). (B) A single cytosine residue transition to thymine (c.492C>T (R44X) in exon 5). (C) A single guanine residue insertion (IVS6+1insG in intron 6). (D) A single guanine residue transversion to cytosine (c.777G>C (A139P) in exon 7). (E) A single adenine residue transition to cytosine (c.779A>C (A139A) in exon 7). (F) A single cytosine residue transition to adenine (c.785C>A (G141G) in exon 7). (G) A single guanine residue transition to adenosine (c.830G>A (W156X) in exon 7).

Table 1.

Clinical features of patients with aniridia and associated anomalies

Patient No.	Age (years)	Sex	Family history					Phenotypes
Patient No.	Age (years)	Sex	Family history	FH^*	N^†	CO^‡	CAT^§	S^Π	G^#	P^**	WT^††	ASD^‡‡	DM^§§
1	34	F	+	+	+	+	+	+	+	-	-	-	+
2	30	M	+	+	+	+	+	+	+	-	-	-	-
3	42	F	-	+	+	+	+	+	-	-	-	-	-
4	40	M	+	+	+	+	+	-	+	-	-	-	-
5	42	M	-	+	+	+	+	-	+	-	-	-	-
6	10	M	-	+	+	+	+	-	-	-	-	-	-
7	18	F	-	+	+	+	+	-	-	-	-	-	-
8	4	F	-	+	+	+	-	+	-	+	+	+	-
9	7	F	+	+	+	+	-	+	-	-	-	-	-
10	10	F	+	+	+	+	-	-	-	-	-	-	-
11	32	M	+	+	+	-	+	+	+	-	-	-	-
12	15	M	+	+	+	-	+	-	-	-	-	-	-

^* FH=foveal hypoplasia

^† N=nystagmus

^‡ CO=corneal opacity

^§ CAT=cataract

^Π S=strabismus

^# G=glaucoma

^** P=ptosis

^†† WT=Wilms tumor

^‡‡ ASD=atrial septal defect

^§§ DM=diabetes mellitus.

Table 2.

Molecular analysis of PAX6 mutations with their predicted products

Exon/Intron	Systematic name	Codon	Type of mutation	Predicted amino acid change	Patient number	References
Exon 5	c.414G>C	18	Missense	Glycine to Arginine	5, 6	Novel
Exon 5	c.492C>T	44	Nonsense	Arginine to stop codon	1, 4, 9, 10	Reported
Intron 6	IVS6+1insG		Insertion	Splicing error	11	Novel
Exon 7	c.777G>C	139	Missense	Alanine to Proline	8	Novel
Exon 7	c.779A>C	139	Transition	Silent mutation	3, 12	Novel
Exon 7	c.785C>A	141	Transition	Silent mutation	2	Novel
Exon 7	c.830G>A	156	Nonsense	Tryptophan to stop codon	7	Reported

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