Nature Genetics
8, 251 - 255 (1994)
doi:10.1038/ng1194-251
Waardenburg syndrome type 2 caused by mutations in the human microphthalmia (MITF) geneMayada Tassabehji1, Valeria E. Newton2
& Andrew P. Read1, 3
1Department of Medical Genetics, St. Mary's Hospital, Manchester M13 0JH, UK
2Centre for Audiology, University of Manchester, Manchester M13 9PL, UK
3Correspondence should be addressed to A.P.R. 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.
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