Identification and functional analysis of a novel mutation in the PAX3 gene associated with Waardenburg syndrome type I

Gene. 2018 Feb 5:642:362-366. doi: 10.1016/j.gene.2017.11.035. Epub 2017 Nov 20.


Waardenburg syndrome type 1 (WS1) is a rare autosomal dominant genetic disorder of neural crest cells (NCC) characterized by congenital sensorineural hearing loss, dystopia canthorum, and abnormal iris pigmentation. WS1 is due to loss-of-function mutations in paired box gene 3 (PAX3). Here, we identified a novel PAX3 mutation (c.808C>G, p.R270G) in a three-generation Chinese family with WS1, and then analyzed its in vitro activities. The R270G PAX3 retained nuclear distribution and normal DNA-binding ability; however, it failed to activate MITF promoter, suggesting that haploinsufficiency may be the underlying mechanism for the mild WS1 phenotype of the study family.

Keywords: Haploinsufficiency; Mutation; PAX3; Sensorineural hearing loss; Waardenburg syndrome.

MeSH terms

  • Cell Line
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Microphthalmia-Associated Transcription Factor / genetics
  • Mutation, Missense*
  • PAX3 Transcription Factor / genetics*
  • PAX3 Transcription Factor / metabolism*
  • Pedigree
  • Promoter Regions, Genetic
  • Sequence Analysis, DNA
  • Waardenburg Syndrome / genetics*
  • Waardenburg Syndrome / metabolism


  • MITF protein, human
  • Microphthalmia-Associated Transcription Factor
  • PAX3 Transcription Factor
  • PAX3 protein, human