Inherited PAX6, NF1 and OTX2 mutations in a child with microphthalmia and aniridia

Eur J Hum Genet. 2007 Aug;15(8):898-901. doi: 10.1038/sj.ejhg.5201826. Epub 2007 Apr 4.


A girl with aniridia, microphthalmia, microcephaly and café au lait macules was found to have mutations in PAX6, NF1 and OTX2. A novel PAX6 missense mutation (p.R38W) was inherited from her mother whose iris phenotype had not been evident because of ocular neurofibromatosis. Analysis of the NF1 gene in the proband, prompted by the mother's diagnosis and the presence of café au lait spots, revealed a nonsense mutation (p.R192X). Subsequently an OTX2 nonsense mutation (p.Y179X) was identified and shown to be inherited from her father who was initially diagnosed with Leber's congenital amaurosis. Since individual mutations in PAX6, OTX2 or NF1 can cause a variety of severe developmental defects, the proband's phenotype is surprisingly mild. This case shows that patients with complex phenotypes should not be eliminated from subsequent mutation analysis after one or even two mutations are found.

Publication types

  • Case Reports

MeSH terms

  • Amino Acid Substitution
  • Aniridia / genetics*
  • Child, Preschool
  • Eye Proteins / genetics*
  • Female
  • Homeodomain Proteins / genetics*
  • Humans
  • Male
  • Microphthalmos / genetics*
  • Neurofibromin 1 / genetics*
  • Otx Transcription Factors / genetics*
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors / genetics*
  • Pedigree
  • Repressor Proteins / genetics*


  • Eye Proteins
  • Homeodomain Proteins
  • Neurofibromin 1
  • OTX2 protein, human
  • Otx Transcription Factors
  • PAX6 Transcription Factor
  • PAX6 protein, human
  • Paired Box Transcription Factors
  • Repressor Proteins