Missense mutations in the DNA-binding region and termination codon in PAX6

Hum Mutat. 2003 Feb;21(2):138-45. doi: 10.1002/humu.10163.


We have identified nine novel intragenic mutations of the PAX6 gene in 30 patients with aniridia. One patient with Wilms' tumor, aniridia, genitourinary anomalies, and mental retardation (WAGR syndrome) had deletion of 11p and had lost the paternal PAX6 allele. Two patients had small deletions: a frameshift that should result in early termination of the PAX6 protein, and a frameshift that leads to a termination-site change and run-on into the 3' untranslated region (UTR). The other 27 patients had single base-pair mutations. Four had splicing defects; three had IVS6+1G>A, which was at a mutation hotspot in the PAX6 gene; 10 had premature termination (four 1024C>T [R203X], also at a mutation hotspot); and six had missense mutations. Missense mutation A321T (1378G>A) was a polymorphic change; the other five missense mutations were L46R, C52R, I56T, G73D, and I87K. These five codons are in the PAX6 paired domain and are highly conserved throughout the entire paired family. Seven patients had a mutation in the normal stop codon (TAA). This change leads to run-on into the 3' UTR and is also at a mutation hotspot. All 30 mutations should result in PAX6 haploinsufficiency. No correlation was observed between mutation sites and phenotypes.

Publication types

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

MeSH terms

  • 3' Untranslated Regions / genetics
  • 3T3 Cells
  • Alternative Splicing / genetics
  • Animals
  • Aniridia / genetics
  • Binding Sites / genetics
  • Cell Line
  • Chromosome Deletion
  • Codon, Terminator / genetics*
  • Eye Proteins
  • Female
  • Frameshift Mutation / genetics
  • Homeodomain Proteins / genetics*
  • Humans
  • Male
  • Mice
  • Mutation, Missense / genetics*
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors
  • Repressor Proteins
  • WAGR Syndrome / genetics


  • 3' Untranslated Regions
  • Codon, Terminator
  • Eye Proteins
  • Homeodomain Proteins
  • PAX6 Transcription Factor
  • PAX6 protein, human
  • Paired Box Transcription Factors
  • Pax6 protein, mouse
  • Repressor Proteins