WAARDENBURG SYNDROME TYPE-2 CAUSED BY MUTATIONS IN THE HUMAN MICROPHTHALMIA (MITF) GENE

Waardenburg syndrome type 2 (WS2) is a dominantly inherited syndrome o f hearing loss and pigmentary disturbances. We recently mapped a WS2 g ene to chromosome 3p12.3-p14.1 and proposed as a candidate gene MITF, the human homologue of the mouse microphthalmia (mi) gene. This encode s a putative basic-helix-loop-helix-leucine zipper transcription facto r expressed in adult skin and in embryonic retina, otic vesicle and ha ir 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 indi viduals in two WS2 families have mutations affecting splice sites in t he MITF gene.