Effect of the Mutant Microphthalmia-Associated Transcription Factor Found in Tietz Syndrome on the In Vitro Development of Mast CellsShigemura, Tomonari MD; Shiohara, Masaaki MD; Tanaka, Miyuki MD; Takeuchi, Kouichi MD; Koike, Kenichi MD, PhDJournal of Pediatric Hematology/Oncology: August 2010 - Volume 32 - Issue 6 - pp 442-447 doi: 10.1097/MPH.0b013e3181d9da5d Original Articles Abstract Author Information Abstract 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. Author Information Department of Pediatrics, Shinshu University School of Medicine, Asahi, Matsumoto, Japan Reprints: Masaaki Shiohara, MD, Department of Pediatrics, Shinshu University School of Medicine, 3-1-1, Asahi, Matsumoto, 390-8621 Japan (e-mail: email@example.com). Received for publication July 1, 2009; accepted January 7, 2010 © 2010 Lippincott Williams & Wilkins, Inc.