The Indian Journal of Pediatrics

, Volume 76, Issue 5, pp 513–517 | Cite as

Genotype/phenotype association in Indian congenital aniridia

  • Guruswamy Neethirajan
  • Abraham Solomon
  • Subbaiah Ramasamy Krishnadas
  • Perumalsamy Vijayalakshmi
  • Periasamy Sundaresan
Special Article

Abstract

The developmental birth eye disorder of iris is known as aniridia. Heterozygous PAX6 gene, which causes human aniridia and small eye in mice, is located on chromosome 11p13. The variability had been documented between the affected individuals within the families, is due to genotypic variation. Haploinsufficiency renders PAX6 allele non-functional or amorphic, however it presents hypomorphic or neomorphic alleles. India is not a well-studied ethnic group, hence the focus on congenital aniridia gene analysis supports the literature and the phenotypic association were analysed both in sporadic as well as familial. The consistent association of truncating PAX6 mutations with the phenotype is owing to non-sense-mediated decay (NMD). It is presumed that the genetic impact of increased homozygosity and heterozygocity in Indian counter part arises as the consequence of consanguineous marriages. The real fact involved in congenital aniridia with other related phenotypes with PAX6 mutations are still controversial.

Key Words

Aniridia PAX6 Amorphic Hypomorphic Marfan’s syndrome Ectopia lentis Sclerocornea 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Shaw MW, Falls HF, Neel JV. Congenital aniridia. Am J Hum Genet 1960; 12:389–415.PubMedGoogle Scholar
  2. 2.
    Glaser T, Walton DS, Maas RL. Genomic structure, evolutionary conservation and aniridia mutations in the human PAX6 gene. Nat Genet 1992; 2:232–239.PubMedCrossRefGoogle Scholar
  3. 3.
    Churchill A, Booth A. Genetics of aniridia and anterior segment dysgenesis. Br J Ophthalmol 1996; 80:669–673.PubMedCrossRefGoogle Scholar
  4. 4.
    Glaser T, Jepeal L, Edwards JG et al. PAX6 gene dosage effect in a family with congenital cataracts, aniridia, anophthalmia and central nervous system defects. Nat Genet 1994; 7:463–471.PubMedCrossRefGoogle Scholar
  5. 5.
    Ton CC, Hirvonen H, Miwa H et al. Positional cloning and characterization of a paired-box and homeobox-containing gene from the aniridia region. Cell 1991; 67:1059–1074.PubMedCrossRefGoogle Scholar
  6. 6.
    Hanson IM, Seawright A, Hardman K et al. PAX6 mutations in aniridia. Hum Mol Genet 1993; 2:915–920.PubMedCrossRefGoogle Scholar
  7. 7.
    Wilson DS, Guenther B, Desplan C et al. High resolution crystal structure of a paired (PAX) class cooperative homeodomain dimer on DNA. Cell 1995; 82:709–719.PubMedCrossRefGoogle Scholar
  8. 8.
    Xu HE, Rould MA, Xu W et al. Crystal structure of the human PAX6 paired domain-DNA complex reveals specific roles for the linker region and carboxy-terminal subdomain in DNA-binding. Genes Dev 1999; 13:1263–1275.PubMedCrossRefGoogle Scholar
  9. 9.
    Simpson TI, Price DJ. PAX6, a pleiotropic player in development. Bioassays 2002; 24:1041–1051.CrossRefGoogle Scholar
  10. 10.
    Tzoulaki I, White IMS, Hanson IM. PAX6 mutations: genotype-phenotype correlations. BMC Genetics 2005; 6:27–39.PubMedCrossRefGoogle Scholar
  11. 11.
    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; 72:1565–1570.PubMedCrossRefGoogle Scholar
  12. 12.
    Song SJ, Liu YZ, Cong RC et al. PAX6 mutation caused brain abnormalities in humans. Beijing Da Xue Xue Bao 2005; 37:48–50PubMedGoogle Scholar
  13. 13.
    Nallathambi J, Neethirajan G, Shashikant S et al. PAX6 missense mutations associated in patients with optic nerve malformation. Mol Vis 2006; 12:236–242.PubMedGoogle Scholar
  14. 14.
    Neethirajan G, Hanson IM, Krishnadas SR et al. A novel PAX6 gene mutation in an Indian aniridia patient. Mol Vis 2003; 9:205–209.PubMedGoogle Scholar
  15. 15.
    Nelson LB, Spaeth GL, Nowinski TS et al. Aniridia: a review. Surv Ophthalmol 1984; 26:621–642.CrossRefGoogle Scholar
  16. 16.
    Neethirajan G, Krishnadas SR, Vijayalakshmi P et al. PAX6 gene variations associated with aniridia in south India. BMC Med Genet 2004; 5:9.PubMedCrossRefGoogle Scholar
  17. 17.
    Neethirajan G, Collinson JM, Krishnadas SR et al. De novo deletions in the paired domain of PAX6 in south Indian aniridic patients. J Hum Genet 2004; 49:647–649.PubMedCrossRefGoogle Scholar
  18. 18.
    Neethirajan G, Nallathambi J, Krishnadas SR et al. Identification of novel mutant PAX6 alleles in Indian cases of familial aniridia. BMC Ophthalmol 2006; 6:28PubMedCrossRefGoogle Scholar
  19. 19.
    van Heyningen V, Williamson KA. PAX6 in sensory development. Hum Mol Genet 2002; 11:1161–1167.PubMedCrossRefGoogle Scholar
  20. 20.
    Chao LY, Mishra R, Strong LC et al. Missense mutations in the DNA-binding region and termination codon in PAX6. Hum Mutat 2003; 21:138–145.PubMedCrossRefGoogle Scholar
  21. 21.
    Negishi K, Azuma N, Yamada M. Various phenotypic expressions of familial aniridia with a PAX6 mutation. Br J Ophthalmol 1999; 83:991–992.PubMedCrossRefGoogle Scholar
  22. 22.
    Chao LY, Mishra R, Strong LC et al. Missense mutations in the DNA-binding region and termination codon in PAX6. Hum Mutat 2003; 21:138–145.PubMedCrossRefGoogle Scholar
  23. 23.
    Gupta SK, De Becker I, Tremblay F et al. Genotype/phenotype correlations in aniridia. Am J Ophthalmol 1998; 126: 203–210.PubMedCrossRefGoogle Scholar
  24. 24.
    Byers PH. Killing the messenger: new insights into nonsense-mediated mRNA decay. J Clin Invest 2002; 109:3–6.PubMedGoogle Scholar
  25. 25.
    Gronskov K, Olsen JH, Sand A et al. Population-based risk estimates of Wilms tumor in sporadic aniridia: a comprehensive mutation screening procedure of PAX6 identifies 80% of mutations in aniridia. Hum Genet 2001; 109:11–18.PubMedCrossRefGoogle Scholar

Copyright information

© Dr. K C Chaudhuri Foundation 2009

Authors and Affiliations

  • Guruswamy Neethirajan
    • 1
    • 4
    • 5
  • Abraham Solomon
    • 1
  • Subbaiah Ramasamy Krishnadas
    • 2
  • Perumalsamy Vijayalakshmi
    • 3
  • Periasamy Sundaresan
    • 4
  1. 1.Department of OphthalmologyHebrew University Medical Center JerusalemJerusalemIsrael
  2. 2.Department of GlaucomaAravind Eye HospitalMaduraiIndia
  3. 3.Department of Pediatric Ophthalmology and StrabismusAravind Eye HospitalMaduraiIndia
  4. 4.Department of GeneticsAravind Medical Research FoundationMaduraiIndia
  5. 5.Department of BiotechnologyAlagappa, UniversityTamilnaduIndia
  6. 6.Department of OphthalmologyHebrew University Medical CenterMaduraiIndia

Personalised recommendations