Homozygosity for Waardenburg syndrome

Am J Hum Genet. 1995 May;56(5):1173-8.


In a large kindred including many individuals affected with Waardenburg (WS) type 1 (WS1) syndrome, a child affected with a very severe form of WS type 3 was born. This child presented with dystopia canthorum, partial albinism, and very severe upper-limb defects. His parents were first cousins, both affected with a mild form of WS1. Molecular analysis of PAX3, the gene that was determined by linkage to cause the disorder in the family, demonstrated a novel missense mutation (S84F) in exon 2 of PAX3 within the paired box. While individuals affected with WS1 were heterozygous for the mutation, the child with WS3 was homozygous for S84F. The observation that the PAX3 homozygote in humans may allow life at least in early infancy and does not cause neural tube defects was unexpected, since, in all the mutations known in mice (splotch), homozygosity has led to severe neural tube defects and intrauterine or neonatal death.

Publication types

  • Case Reports

MeSH terms

  • Base Sequence
  • DNA-Binding Proteins / genetics*
  • Female
  • Genetic Linkage
  • Homozygote*
  • Humans
  • Male
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • PAX3 Transcription Factor
  • Paired Box Transcription Factors
  • Pedigree
  • Polymerase Chain Reaction
  • Sequence Analysis, DNA
  • Transcription Factors*
  • Waardenburg Syndrome / genetics*


  • DNA-Binding Proteins
  • PAX3 Transcription Factor
  • PAX3 protein, human
  • Paired Box Transcription Factors
  • Transcription Factors
  • Pax3 protein, mouse