Mutations in the paired domain of the human PAX3 gene cause Klein-Waardenburg syndrome (WS-III) as well as Waardenburg syndrome type I (WS-I)

Am J Hum Genet. 1993 Mar;52(3):455-62.


Waardenburg syndrome type I (WS-I) is an autosomal dominant disorder characterized by sensorineural hearing loss, dystopia canthorum, pigmentary disturbances, and other developmental defects. Klein-Waardenburg syndrome (WS-III) is a disorder with many of the same characteristics as WS-I and includes musculoskeletal abnormalities. We have recently reported the identification and characterization of one of the first gene defects, in the human PAX3 gene, which causes WS-I. PAX3 is a DNA-binding protein that contains a structural motif known as the paired domain and is believed to regulate the expression of other genes. In this report we describe two new mutations, in the human PAX3 gene, that are associated with WS. One mutation was found in a family with WS-I, while the other mutation was found in a family with WS-III. Both mutations were in the highly conserved paired domain of the human PAX3 gene and are similar to other mutations that cause WS. The results indicate that mutations in the PAX3 gene can cause both WS-I and WS-III.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cloning, Molecular
  • Cosmids
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics*
  • Exons
  • Female
  • Gene Library
  • Humans
  • Male
  • Mice
  • Molecular Sequence Data
  • Mutation*
  • Oligodeoxyribonucleotides
  • PAX3 Transcription Factor
  • Paired Box Transcription Factors
  • Pedigree
  • Polymerase Chain Reaction / methods
  • Protein Structure, Secondary
  • Sequence Homology, Amino Acid
  • Transcription Factors*
  • Waardenburg Syndrome / genetics*


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

Associated data

  • GENBANK/L07482
  • GENBANK/L07483