Genetic and phenotypic heterogeneity in Chinese patients with Waardenburg syndrome type II

PLoS One. 2013 Oct 23;8(10):e77149. doi: 10.1371/journal.pone.0077149. eCollection 2013.


Waardenburg Syndrome (WS) is an autosomal-dominant disorder characterized by sensorineural hearing loss and pigmentary abnormalities of the eyes, hair, and skin. Microphthalmia-associated transcription factor (MITF) gene mutations account for about 15% of WS type II (WS2) cases. To date, fewer than 40 different MITF gene mutations have been identified in human WS2 patients, and few of these were of Chinese descent. In this study, we report clinical findings and mutation identification in the MITF gene of 20 Chinese WS2 patients from 14 families. A high level of clinical variability was identified. Sensorineural hearing loss (17/20, 85.0%) and heterochromia iridum (20/20, 100.0%) were the most commonly observed clinical features in Chinese WS2 patients. Five affected individuals (5/20, 25.0%) had numerous brown freckles on the face, trunk, and limb extremities. Mutation screening of the MITF gene identified five mutations: c.20A>G, c.332C>T, c.647_649delGAA, c.649A>G, and c.763C>T. The total mutational frequency of the MITF gene was 21.4% (3/14), which is significantly higher than the 15.0% observed in the fair-skinned WS2 population. Our results indicate that MITF mutations are relatively common among Chinese WS2 patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asian People / genetics*
  • Base Sequence
  • Computational Biology
  • DNA Mutational Analysis
  • Genetic Heterogeneity*
  • Hearing Loss, Sensorineural / pathology
  • Humans
  • Iris Diseases / pathology
  • Microphthalmia-Associated Transcription Factor / genetics*
  • Molecular Sequence Data
  • Pedigree
  • Phenotype*
  • Pigmentation Disorders / pathology
  • Waardenburg Syndrome / genetics*
  • Waardenburg Syndrome / pathology*


  • MITF protein, human
  • Microphthalmia-Associated Transcription Factor

Supplementary concepts

  • Heterochromia iridis
  • Waardenburg syndrome type 2

Grants and funding

These investigations were supported by grants from the Key Project of National Natural Science Foundation of China (81030017), National Natural Science Foundation for Distinguished Young Scholars (81125008) and The National Basic Research Program of China (973 Program) (2013CB945402) to HY, a grant from The National Basic Research Program of China (973 Program) (2012CB967900) to Shiming Yang, and a grant from the National Natural Science Foundation of China (81200752) to Shuzhi Yang. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.