Waardenburg syndrome type 2 caused by mutations in the human microphthalmia (MITF) gene

Nat Genet. 1994 Nov;8(3):251-5. doi: 10.1038/ng1194-251.


Waardenburg syndrome type 2 (WS2) is a dominantly inherited syndrome of hearing loss and pigmentary disturbances. We recently mapped a WS2 gene to chromosome 3p12.3-p14.1 and proposed as a candidate gene MITF, the human homologue of the mouse microphthalmia (mi) gene. This encodes a putative basic-helix-loop-helix-leucine zipper transcription factor expressed in adult skin and in embryonic retina, otic vesicle and hair follicles. Mice carrying mi mutations show reduced pigmentation of the eyes and coat, and with some alleles, microphthalmia, hearing loss, osteopetrosis and mast cell defects. Here we show that affected individuals in two WS2 families have mutations affecting splice sites in the MITF gene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Chromosomes, Human, Pair 3
  • DNA-Binding Proteins / genetics*
  • Disease Models, Animal
  • Eye Color / genetics
  • Genes*
  • Hair Color / genetics
  • Haplotypes / genetics
  • Hearing Loss, Sensorineural / genetics
  • Helix-Loop-Helix Motifs
  • Humans
  • Leucine Zippers
  • Mice
  • Mice, Mutant Strains
  • Microphthalmia-Associated Transcription Factor
  • Microphthalmos / genetics
  • Molecular Sequence Data
  • Pedigree
  • RNA Splicing*
  • Transcription Factors*
  • Transcription, Genetic / genetics*
  • Waardenburg Syndrome / genetics*


  • DNA-Binding Proteins
  • MITF protein, human
  • Microphthalmia-Associated Transcription Factor
  • Mitf protein, mouse
  • Transcription Factors