Mutations in microphthalmia-associated transcription factor (MITF) lead to 
Waardenburg syndrome type 2 (WS2), a dominantly inherited disorder involving 
hearing loss and pigment disturbances caused by a lack of melanocytes. On rare 
occasions, mutations in MITF lead to Tietz syndrome (TS), which is characterized 
by a severe WS2 phenotype. The MITF gene is the human homolog of the mouse 
microphthalmia (mi) gene in some families. Mi/mi mice show decreased numbers and 
an abnormal phenotype of mast cells (MC). In contrast, the number and phenotype 
of MC in WS2/TS patients who also have an alteration in their MITF gene are 
unclear. In this study, we identified a mutation in the MITF gene, delR217, 
which was equivalent to that found in mi/mi mice, in a case of TS. None of the 
MITF isoforms with the mutation were able to transactivate the tyrosinase gene 
promoter. In addition, mutant MITF-M showed dominant negative activity toward 
wild-type MITF-M, inhibiting its transactivation of the tyrosinase gene 
promoter. The patient's peripheral blood CD34 cells showed no differences with 
respect to total cell number or their expression levels of tryptase mRNA in a 
serum-deprived liquid culture system for 6 weeks when compared with normal 
control cells. These findings suggest that MITF does not play a critical role in 
MC development in humans.