Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (69)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Hanson, I.
Right arrow Articles by van Heyningen, V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hanson, I.
Right arrow Articles by van Heyningen, V.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Human Molecular Genetics, Vol 8, 165-172, Copyright © 1999 by Oxford University Press

ARTICLES

Missense mutations in the most ancient residues of the PAX6 paired domain underlie a spectrum of human congenital eye malformations

I Hanson, A Churchill, J Love, R Axton, T Moore, M Clarke, F Meire and V van Heyningen
MRC Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK. isabel.hanson@hgu.mrc.ac.uk

Mutations of the human PAX6 gene underlie aniridia (congenital absence of the iris), a rare dominant malformation of the eye. The spectrum of PAX6 mutations in aniridia patients is highly biased, with 92% of all reported mutations leading to premature truncation of the protein (nonsense, splicing, insertions and deletions) and just 2% leading to substitution of one amino acid by another (missense). The extraordinary conservation of the PAX6 protein at the amino acid level amongst vertebrates predicts that pathological missense mutations should in fact be common even though they are hardly ever seen in aniridia patients. This indicates that there is a heavy ascertainment bias in the selection of patients for PAX6 mutation analysis and that the 'missing' PAX6 missense mutations frequently may underlie phenotypes distinct from textbook aniridia. Here we present four novel PAX6 missense mutations, two in association with atypical phenotypes: ectopia pupillae (displaced pupils) and congenital nystagmus (searching gaze), and two in association with more recognizable aniridia phenotypes. Strikingly, all four mutations are located within the PAX6 paired domain and affect amino acids which are highly conserved in all known paired domain proteins. Our results support the hypothesis that the under-representation of missense mutations is caused by ascertainment bias and suggest that a substantial burden of PAX6 - related disease remains to be uncovered.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 IOVSHome page
S. A. Chanas, J. M. Collinson, T. Ramaesh, N. Dora, D. A. Kleinjan, R. E. Hill, and J. D. West
Effects of Elevated Pax6 Expression and Genetic Background on Mouse Eye Development
Invest. Ophthalmol. Vis. Sci., September 1, 2009; 50(9): 4045 - 4059.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
M. Hingorani, K. A. Williamson, A. T. Moore, and V. van Heyningen
Detailed Ophthalmologic Evaluation of 43 Individuals with PAX6 Mutations
Invest. Ophthalmol. Vis. Sci., June 1, 2009; 50(6): 2581 - 2590.
[Abstract] [Full Text] [PDF]

Home page
 Arch OphthalmolHome page
C. Bredrup, P. M. Knappskog, E. Rodahl, and H. Boman
Clinical Manifestation of a Novel PAX6 Mutation Arg128Pro
Arch Ophthalmol, March 1, 2008; 126(3): 428 - 430.
[Full Text] [PDF]

Home page
 IOVSHome page
S. Li, D. Goldowitz, and D. J. Swanson
The Requirement of Pax6 for Postnatal Eye Development: Evidence from Experimental Mouse Chimeras
Invest. Ophthalmol. Vis. Sci., July 1, 2007; 48(7): 3292 - 3300.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
D. Bandah, T. Swissa, G. Ben-Shlomo, E. Banin, R. Ofri, and D. Sharon
A Complex Expression Pattern of Pax6 in the Pigeon Retina
Invest. Ophthalmol. Vis. Sci., June 1, 2007; 48(6): 2503 - 2509.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
E. A. Kim, Y. T. Noh, M.-J. Ryu, H.-T. Kim, S.-E. Lee, C.-H. Kim, C. Lee, Y. H. Kim, and C. Y. Choi
Phosphorylation and Transactivation of Pax6 by Homeodomain-interacting Protein Kinase 2
J. Biol. Chem., March 17, 2006; 281(11): 7489 - 7497.
[Abstract] [Full Text] [PDF]

Home page
 Br J OphthalmolHome page
P K F Addison, V Berry, A C W Ionides, P J Francis, S S Bhattacharya, and A T Moore
Posterior polar cataract is the predominant consequence of a recurrent mutation in the PITX3 gene
Br J Ophthalmol, February 1, 2005; 89(2): 138 - 141.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
S. Aijaz, B. J. Clark, K. Williamson, V. van Heyningen, D. Morrison, D. FitzPatrick, R. Collin, N. Ragge, A. Christoforou, A. Brown, et al.
Absence of SIX6 Mutations in Microphthalmia, Anophthalmia, and Coloboma
Invest. Ophthalmol. Vis. Sci., November 1, 2004; 45(11): 3871 - 3876.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
H. N. Cinar and A. D. Chisholm
Genetic Analysis of the Caenorhabditis elegans pax-6 Locus: Roles of Paired Domain-Containing and Nonpaired Domain-Containing Isoforms
Genetics, November 1, 2004; 168(3): 1307 - 1322.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
B Pal, M D Mohamed, T J Keen, G A Williams, J A Bradbury, E Sheridan, and C F Inglehearn
A new phenotype of recessively inherited foveal hypoplasia and anterior segment dysgenesis maps to a locus on chromosome 16q23.2-24.2.
J. Med. Genet., October 1, 2004; 41(10): 772 - 777.
[Full Text] [PDF]

Home page
 J. Med. Genet.Home page
V Berry, Z Yang, P K F Addison, P J Francis, A Ionides, G Karan, L Jiang, W Lin, J Hu, R Yang, et al.
Recurrent 17 bp duplication in PITX3 is primarily associated with posterior polar cataract (CPP4)
J. Med. Genet., August 1, 2004; 41(8): e109 - e109.
[Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
J. E. Ploski, M. K. Shamsher, and A. Radu
Paired-Type Homeodomain Transcription Factors Are Imported into the Nucleus by Karyopherin 13
Mol. Cell. Biol., June 1, 2004; 24(11): 4824 - 4834.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
B. K. Chauhan, Y. Yang, K. Cveklova, and A. Cvekl
Functional interactions between alternatively spliced forms of Pax6 in crystallin gene regulation and in haploinsufficiency
Nucleic Acids Res., March 12, 2004; 32(5): 1696 - 1709.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
B. K. Chauhan, Y. Yang, K. Cveklova, and A. Cvekl
Functional Properties of Natural Human PAX6 and PAX6(5a) Mutants
Invest. Ophthalmol. Vis. Sci., February 1, 2004; 45(2): 385 - 392.
[Abstract] [Full Text] [PDF]

Home page
 Cereb CortexHome page
D. A. Tyas, H. Pearson, P. Rashbass, and D. J. Price
Pax6 Regulates Cell Adhesion during Cortical Development
Cereb Cortex, June 1, 2003; 13(6): 612 - 619.
[Abstract] [Full Text] [PDF]

Home page
 Br J OphthalmolHome page
R V Jamieson, F Munier, A Balmer, N Farrar, R Perveen, and G C M Black
Pulverulent cataract with variably associated microcornea and iris coloboma in a MAF mutation family
Br J Ophthalmol, April 1, 2003; 87(4): 411 - 412.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
R. Mishra, I. P. Gorlov, L. Y. Chao, S. Singh, and G. F. Saunders
PAX6, Paired Domain Influences Sequence Recognition by the Homeodomain
J. Biol. Chem., December 13, 2002; 277(51): 49488 - 49494.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
T. Borras, C. R. Brandt, R. Nickells, and R. Ritch
Gene Therapy for Glaucoma: Treating a Multifaceted, Chronic Disease
Invest. Ophthalmol. Vis. Sci., August 1, 2002; 43(8): 2513 - 2518.
[Full Text] [PDF]

Home page
 Br J OphthalmolHome page
M G Wirth, I M Russell-Eggitt, J E Craig, J E Elder, and D A Mackey
Aetiology of congenital and paediatric cataract in an Australian population
Br J Ophthalmol, July 1, 2002; 86(7): 782 - 786.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
V. van Heyningen and K. A. Williamson
PAX6 in sensory development
Hum. Mol. Genet., May 15, 2002; 11(10): 1161 - 1167.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
J. Favor, H. Peters, T. Hermann, W. Schmahl, B. Chatterjee, A. Neuhauser-Klaus, and R. Sandulache
Molecular Characterization of Pax62Neu Through Pax610Neu: An Extension of the Pax6 Allelic Series and the Identification of Two Possible Hypomorph Alleles in the Mouse Mus musculus
Genetics, December 1, 2001; 159(4): 1689 - 1700.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
S. Singh, L. Y. Chao, R. Mishra, J. Davies, and G. F. Saunders
Missense mutation at the C-terminus of PAX6 negatively modulates homeodomain function
Hum. Mol. Genet., April 1, 2001; 10(9): 911 - 918.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J. D. Lauderdale, J. S. Wilensky, E. R. Oliver, D. S. Walton, and T. Glaser
3' deletions cause aniridia by preventing PAX6 gene expression
PNAS, November 16, 2000; (2000) 240398797.
[Abstract] [Full Text]

Home page
 IOVSHome page
R. Perveen, I. C. Lloyd, J. Clayton–Smith, A. Churchill, V. van Heyningen, I. Hanson, D. Taylor, C. McKeown, M. Super, B. Kerr, et al.
Phenotypic Variability and Asymmetry of Rieger Syndrome Associated with PITX2 Mutations
Invest. Ophthalmol. Vis. Sci., August 1, 2000; 41(9): 2456 - 2460.
[Abstract] [Full Text]

Home page
 Hum Mol GenetHome page
J. Dixon, C. Brakebusch, R. Fassler, and M. J. Dixon
Increased levels of apoptosis in the prefusion neural folds underlie the craniofacial disorder, Treacher Collins syndrome
Hum. Mol. Genet., June 12, 2000; 9(10): 1473 - 1480.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
N. Fonknechten, D. Mavel, P. Byrne, C.-S. Davoine, C. Cruaud, D. Boentsch, D. Samson, P. Coutinho, M. Hutchinson, P. M. Monagle, et al.
Spectrum of SPG4 mutations in autosomal dominant spastic paraplegia
Hum. Mol. Genet., March 1, 2000; 9(4): 637 - 644.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
M. K. Duncan, A. Cvekl, X. Li, and J. Piatigorsky
Truncated Forms of Pax-6 Disrupt Lens Morphology in Transgenic Mice
Invest. Ophthalmol. Vis. Sci., February 1, 2000; 41(2): 464 - 473.
[Abstract] [Full Text]

Home page
 J. Cell Sci.Home page
M. Duncan, Z Kozmik, K Cveklova, J Piatigorsky, and A Cvekl
Overexpression of PAX6(5a) in lens fiber cells results in cataract and upregulation of (alpha)5(beta)1 integrin expression
J. Cell Sci., January 9, 2000; 113(18): 3173 - 3185.
[Abstract] [PDF]

Home page
 Br J OphthalmolHome page
G C M BLACK, M E BOULTON, P N BISHOP, and D McLEOD
Ophthalmology in the post-genomic era
Br J Ophthalmol, November 1, 1999; 83(11): 1215 - 1218.
[Full Text]

Home page
 Genes Dev.Home page
H. E. Xu, M. A. Rould, W. Xu, J. A. Epstein, R. L. Maas, and C. O. Pabo
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., May 15, 1999; 13(10): 1263 - 1275.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
I. Saadi, E. V. Semina, B. A. Amendt, D. J. Harris, K. P. Murphy, J. C. Murray, and A. F. Russo
Identification of a Dominant Negative Homeodomain Mutation in Rieger Syndrome
J. Biol. Chem., June 15, 2001; 276(25): 23034 - 23041.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J. D. Lauderdale, J. S. Wilensky, E. R. Oliver, D. S. Walton, and T. Glaser
3' deletions cause aniridia by preventing PAX6 gene expression
PNAS, December 5, 2000; 97(25): 13755 - 13759.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.