Waardenburg's syndrome patients have mutations in the human homologue of the Pax-3 paired box gene

doi:doi:10.1038/355635a0

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Nature 355, 635 - 636 (13 February 1992); doi:10.1038/355635a0

Waardenburg's syndrome patients have mutations in the human homologue of the Pax-3 paired box gene

Mayada Tassabehji^*, Andrew P. Read^*†, Valerie E. Newton^‡, Rodney Harris^*, Rudi Balling^§, Peter Gruss & Tom Strachan^*

^*University Department of Medical Genetics, St Mary's Hospital, Manchester M13 OJH, UK
^‡Centre for Audiology, University of Manchester, Oxford Road, Manchester M13 9PL, UK.
^§Max Planck Institute for Immunobiology, D-7800 Freiburg, Germany.
Max Planck Institute for Biophysical Chemistry, D-3400 Göttingen, Germany.
^†To whom correspondence should be addressed.

WAARDENGURG'S syndrome (WS) is an autosomal dominant combination of deafness and pigmentary disturbances, probably caused by defective function of the embryonic neural crest^1,2. We have mapped one gene for WS to the distal part of chromosome 2 (ref. 3). On the basis of their homologous chromosomal location, their close linkage to an alkaline phosphatase gene, and their related phenotype, we suggested that WS and the mouse mutant Splotch^4,5 might be homologous. Splotch is caused by mutation in the mouse Pax-3 gene^6,7. This gene is one of a family of eight Pax genes known in mice which are involved in regulating embryonic development; each contains a highly conserved transcription control sequence, the paired box⁸. Here we show that some families with WS have mutations in the human homologue⁹ of Pax-3. Mutations in a related gene, Pax-6, which, like Pax-3, has both a paired box and a paired-type homeobox sequence, cause the Small-eye mutation in mice¹⁰ and aniridia inman¹¹. Thus mutations in the Pax genes are important causes of human developmental defects.