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Double heterozygous mutations of MITF and PAX3 result in Waardenburg syndrome with increased penetrance in pigmentary defects.

Abstract
Waardenburg syndrome (WS) is characterized by sensorineural hearing loss and pigmentary defects of the hair, skin, and iris. Heterozygous mutations of MITF and its transactivator gene PAX3 are associated with Waardenburg syndrome type II (WS2) and type I (WS1), respectively. Most patients with MITF or PAX3 mutations, however, show variable penetrance of WS-associated phenotypes even within families segregating the same mutation, possibly mediated by genetic background or specific modifiers. In this study, we reported a rare Waardenburg syndrome simplex family in which a pair of WS parents gave birth to a child with double heterozygous mutations of MITF and PAX3. Compared to his parents who carried a single mutation in either MITF or PAX3, this child showed increased penetrance of pigmentary defects including white forelock, white eyebrows and eyelashes, and patchy facial depigmentation. This observation suggested that the expression level of MITF is closely correlated to the penetrance of WS, and variants in transcription regulator genes of MITF may modify the relevant clinical phenotypes.
AuthorsT Yang, X Li, Q Huang, L Li, Y Chai, L Sun, X Wang, Y Zhu, Z Wang, Z Huang, Y Li, H Wu
JournalClinical genetics (Clin Genet) Vol. 83 Issue 1 Pg. 78-82 (Jan 2013) ISSN: 1399-0004 [Electronic] Denmark
PMID22320238 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.
Chemical References
  • MITF protein, human
  • Microphthalmia-Associated Transcription Factor
  • PAX3 Transcription Factor
  • PAX3 protein, human
  • Paired Box Transcription Factors
Topics
  • Child
  • Female
  • Heterozygote
  • Humans
  • Male
  • Microphthalmia-Associated Transcription Factor (genetics)
  • Mutation
  • PAX3 Transcription Factor
  • Paired Box Transcription Factors (genetics)
  • Pedigree
  • Penetrance
  • Phenotype
  • Pigmentation Disorders (genetics, physiopathology)
  • Waardenburg Syndrome (genetics, physiopathology)

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