Functional analysis of a SOX10 gene mutation associated with Waardenburg syndrome II

Biochem Biophys Res Commun. 2017 Nov 4;493(1):258-262. doi: 10.1016/j.bbrc.2017.09.034. Epub 2017 Sep 9.

Abstract

Waardenburg syndrome (WS) is an autosomal dominant inherited non-syndromic type of hereditary hearing loss characterized by varying combinations of sensorineural hearing loss and abnormal pigmentation of the hair, skin, and inner ear. WS is classified into four subtypes (WS1-WS4) based on additional symptoms. WS2 is characterized by the absence of additional symptoms. Recently, we identified a SOX10 missense mutation c.422T > C (p.L141P) associated with WS2. We performed functional assays and found the mutant loses DNA-binding capacity, shows aberrant cytoplasmic and nuclear localization, and fails to interact with PAX3. Therefore, the mutant cannot transactivate the MITF promoter effectively, inhibiting melanin synthesis and leading to WS2. Our study confirmed haploinsufficiency as the underlying pathogenesis for WS2.

Keywords: Functional analysis; L141p; Mutation; SOX10; Waardenburg syndrome.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Haplotypes / genetics*
  • Humans
  • Male
  • Mutation / genetics
  • PAX3 Transcription Factor / genetics*
  • Polymorphism, Single Nucleotide / genetics*
  • SOXE Transcription Factors / genetics*
  • Waardenburg Syndrome / genetics*

Substances

  • PAX3 Transcription Factor
  • PAX3 protein, human
  • SOX10 protein, human
  • SOXE Transcription Factors

Supplementary concepts

  • Waardenburg syndrome type 2