Mutation in the PAX6 gene in twenty patients with aniridia

Hum Mutat. 2000;15(4):332-9. doi: 10.1002/(SICI)1098-1004(200004)15:4<332::AID-HUMU5>3.0.CO;2-1.


This is a report on the nature of the mutations in the PAX6 gene in twenty patients with aniridia. Five of the twenty patients had sporadic aniridia with deletions in chromosome 11p13. Three of the five had WAGR syndrome (Wilms tumor, aniridia, genitourinary anomalies, mental retardation), and the other two had deletions whose breakpoints occurred between the PAX6 and the WT1 genes. Allelic losses at PAX6 were of paternal origin. The remaining fifteen patients with aniridia had intragenic mutations in the PAX6 gene, with mutations found from exon 5 to exon 12. Twelve cases of dysfunctional PAX6 were due to premature termination of the protein by nonsense mutations (five cases), splicing defect (one case), deletion (two cases), deletion-insertions (two cases), and tandem repeat insertions (two cases). One patient (P2) had a PAX6 protein with de novo in-frame deletion of alanine, arginine, and proline at codon positions 37, 38, and 39. These codons are in the paired box region, and codon 38 is in contact with the phosphate group of the sugar-phosphate backbone of the target DNA. Another patient (P8) had a single nucleotide transition at c.1182 (nucleotide number, Genbank accession #M93650, used as in Glaser et al. [1992]), which generated both a missense mutation (Q255H) and a splicing defect. A missense mutation was found at G387E in a third patient (P10). All observed mutations support the notion that haploinsufficiency in PAX6 results in aniridia and associated eye anomalies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aniridia / genetics*
  • Chromosome Deletion
  • Chromosomes, Human, Pair 11 / genetics
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / genetics*
  • Eye Proteins
  • Female
  • Frameshift Mutation
  • Homeodomain Proteins*
  • Humans
  • Male
  • Mutation / genetics*
  • Mutation, Missense
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors
  • Pedigree
  • Phenotype
  • Repressor Proteins
  • Sequence Deletion


  • DNA-Binding Proteins
  • Eye Proteins
  • Homeodomain Proteins
  • PAX6 Transcription Factor
  • PAX6 protein, human
  • Paired Box Transcription Factors
  • Repressor Proteins