Variable phenotype related to a novel PAX 6 mutation (IVS4+5G>C) in a family presenting congenital nystagmus and foveal hypoplasia

Am J Ophthalmol. 2004 Dec;138(6):1016-21. doi: 10.1016/j.ajo.2004.08.003.


Purpose: Several ocular defects have been identified as a consequence of the PAX6 gene mutations. With regard to the implication of this gene in unusual phenotypes, we report a family presenting with congenital nystagmus, foveal hypoplasia, and iris hypoplasia or atypical coloboma.

Design: Observational case report.

Methods: The entire transcribed region of the PAX6 gene was submitted to mutation search at the DNA and mRNA levels in five affected members of a French family in test with 82 normal subjects.

Results: A novel heterozygous PAX6 gene splice mutation (IVS4 + 5G>C) was identified. The mutation is located in IVS4 within the consensus donor splice site. A mutant mRNA lacking exon 4 as the sole defect was evidenced. The resultant protein was predicted to contain a cryptic ATG initiation codon in exon 3 and a slightly altered paired-domain in an open reading frame extended by 13 amino acids.

Conclusions: The association of anterior segment anomalies and foveal hypoplasia with one of the slightest alterations of the PAX6 protein described to date confirms the association of variant phenotypes with hypomorphic alleles. Mutation screening of the PAX6 gene could be useful in elucidating the origin of complex ocular malformations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Base Sequence
  • DNA Mutational Analysis
  • Eye Abnormalities / genetics*
  • Eye Proteins / genetics*
  • Female
  • Fovea Centralis / abnormalities*
  • Homeodomain Proteins / genetics*
  • Humans
  • Infant
  • Iris / abnormalities
  • Molecular Sequence Data
  • Nystagmus, Congenital / genetics*
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors
  • Pedigree
  • Phenotype
  • Point Mutation*
  • Polymorphism, Single-Stranded Conformational
  • RNA Splice Sites / genetics
  • RNA, Messenger / genetics
  • Repressor Proteins
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors / genetics*


  • Eye Proteins
  • Homeodomain Proteins
  • PAX6 Transcription Factor
  • PAX6 protein, human
  • Paired Box Transcription Factors
  • RNA Splice Sites
  • RNA, Messenger
  • Repressor Proteins
  • Transcription Factors