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

PAX6 Mutations and Clinical Features of Congenital Aniridia

Affiliations
  • 1Department of Ophthalmology, Yeungnam University College of Medicine, Daegu, Koera. sccha@med.yu.ac.kr
  • 2Cheil Eye Hospital, Daegu, Koera.

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.

Keyword

Aniridia; Glaucoma; Mutation; PAX6 gene

MeSH Terms

Adult
Aniridia
Clinical Coding
DNA
Genotype
Glaucoma
Humans
Male
Medical Records
Polymerase Chain Reaction
DNA

Figure

  • 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).


Reference

References

1. Grant WM, Walton DS. Progressive changes in the angle in congenital aniridia, with development of glaucoma. Am J Ophthalmol. 1974; 78:842–7.
Article
2. Mackman G, Brightbill FS, Optiz JM. Corneal changes in aniridia. Am J Ophthalmol. 1979; 87:497–502.
Article
3. Nelson LB, Spaeth GL, Nowinski TS, et al. Aniridia:a review. Surv Ophthalmol. 1984; 28:621–42.
4. Churchill A, Booth A. Genetics of aniridia and anterior segment dysgenesis. Br J Ophthalmol. 1996; 80:669–73.
Article
5. Ton CCT, Hirvonen H, Miwa H, et al. Positional cloning and characterization of a paired box- and homeobox-containing gene from the aniridia region. Cell. 1991; 67:1059–74.
Article
6. Glaser T, Walton DS, Maas RL. Genomic structure, evolu- tionary conservation and aniridia mutations in the human PAX6 gene. Nature Genet. 1992; 2:232–9.
7. Neethiranjan G, Krishnadas SR, Vijayalakshmi P, et al. PAX6 gene variations associated with aniridia in south India. BMC Med Genet. 2004; 5:9.
Article
8. Kawano T, Wang C, Hotta Y, et al. Three novel mutations of the PAX6 gene in Japanese aniridia patients. J Hum Genet. 2007; 52:571–4.
Article
9. Prosser J, van Heyningen V. Pax6 mutations reviewed. Hum Mutat. 1998; 11:93–108.
Article
10. Chung SJ. A case of aniridia. J Korean Ophthalmol Soc. 1971; 12:29–30.
11. Hwang YJ, Kim BH, Bae HB, Shim WS. One family of aniridia. J Korean Ophthalmol Soc. 1980; 21:255–9.
12. Hong KY, Chung YT. Twocases of congenital aniridia. J Korean Ophthalmol Soc. 1987; 28:851–7.
13. Ahn CS, Lee JI, Kim YH. Congenital aniridia in a family for three generations. J Korean Ophthalmol Soc. 1990; 31:383–9.
14. Bae JH, Kwak MS, Cho YW. Three cases of congenital aniridia in one family. J Korean Ophthalmol Soc. 2000; 41:282–7.
15. Tzoulaki I, White IMS, Hanson IM. PAX6 mutations: genotype-phenotype correlations. BMC Genet. 2005; 6:27–38.
Article
16. Nachman MW, Crowell SL. Estimate of the mutation rate per nucleotide in humans. Genetics. 2000; 156:297–304.
Article
17. Neuner-Jehle M, Munier F, Kobetz A, et al. Identification of novel PAX6 mutations in two families with bilateral aniridia. Mutations in brief no. 167. Online. Hum Mutat. 1998; 12:138.
18. Brown A, McKie M, van Heyningen V, Prosser J. The human PAX6 mutation database. Nucl Acids Res. 1998; 26:259–64.
Article
19. Vincent MC, Pujo AL, Olivier D, Calvas P. Screening for PAX6 gene mutations is consistent with haploinsufficiency as the main mechanism leading to various ocular defects. Eur J Hum Genet. 2003; 11:163–9.
Article
20. Gupta S, De Becker I, Guernsey D, Neuman P. Polymerase chain reaction-based risk assessment for Wilms tumor in sporadic aniridia. Am J Ophthalmol. 1998; 125:687–92.
Article
21. Churchill A, Hansom I, Markham A. Prenatal diagnosis of aniridia. Ophthalmology. 2000; 107:1153–6.
22. Graziano C, D’Elia AV, Mazzanti L, et al. A de novo nonsense mutation of PAX6 gene in a patient with aniridia, ataxia, and mental retardation. Am J Med Genet A. 2007; 143:1802–5.
23. Adachi M, Dickens CJ, Hetherington J Jr., et alClinical experience of trabeculectomy for the surgical treatment of aniridic glaucoma. Ophthalmology. 1997; 104:2121–5.
24. Grøønskov K, Rosenberg T, Sand A, Brøøndum-Nielsen K. Mutational analysis of PAX6: 16 novel mutations including 5 missense mutations with a mild aniridia phenotype. Eur J Hum Genet. 1999; 7:274–86.
Article
25. Atchaneeyasakul LO, Trinavarat A, Dulayajinda D, et al. Novel and De-novo truncating PAX6 mutations and ocular phenotypes in Thai aniridia patients. Ophthalmic Genetics. 2006; 27:21–7.
26. Azuma N, Yamaguchi Y, Handa H, et al. Mutations of the PAX6 gene detected in patients with a variety of optic-nerve malformations. Am J Hum Genet. 2003; 72:1565–70.
Article
27. Yuan H, Kang Y, Shao Z, et al. Two novel PAX6 mutations identified in northeastern Chinese patients with aniridia. Mol Vis. 2007; 30:1555–61.
28. Tsai YY, Chiang CC, Lin HJ, et al. A PAX6 gene poly- morphism is associated with genetic predisposition to extreme myopia. Eye. 2008; 22:576–81.
Full Text Links
  • JKOS
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr