Identification of six novel variants in Waardenburg syndrome type II by next-generation sequencing

Mol Genet Genomic Med. 2020 Mar;8(3):e1128. doi: 10.1002/mgg3.1128. Epub 2020 Jan 20.


Background: Waardenburg syndrome (WS) is a dominantly inherited, genetically heterogeneous auditory-pigmentary syndrome characterized by nonprogressive sensorineural hearing loss and iris discoloration. This study aimed to investigate the underlying molecular pathology in Chinese WS families.

Methods: A total of 13 patients with Waardenburg syndrome type II (WS2) from six unrelated Chinese families were enrolled. We investigated the mutation profile of genes related to congenital deafness in these families through a targeted sequencing technology and validated the candidate variants by Sanger sequencing.

Results: We identified six novel variants in microphthalmia-associated transcription factor (MITF) and SRY-box 10 (SOX10), which were predicted to be disease causing by in silico analysis. Our results showed that mutations in SOX10 and MITF are two major causes of deafness associated with WS, and de novo mutations were frequently found in probands with SOX10 mutations but not in those with MITF mutations.

Conclusion: Results showed that targeted next-generation sequencing (NGS) enabled us to detect disease-causing mutations with high accuracy, stability, speed and throughput. Our study extends the pathogenic mutation spectrum of MITF and SOX10.

Keywords: MITF; SOX10; Waardenburg syndrome; next-generation sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Female
  • Humans
  • Male
  • Microphthalmia-Associated Transcription Factor / genetics*
  • Middle Aged
  • Mutation*
  • SOXE Transcription Factors / genetics*
  • Waardenburg Syndrome / genetics*
  • Waardenburg Syndrome / pathology


  • MITF protein, human
  • Microphthalmia-Associated Transcription Factor
  • SOX10 protein, human
  • SOXE Transcription Factors

Supplementary concepts

  • Waardenburg syndrome type 2