Mutation of the KIT (mast/stem cell growth factor receptor) protooncogene in human piebaldism

Piebaldism is an autosomal dominant genetic disorder characterized by cogenital patches of skin and hair from which melanocytes are completely absent. A similar disorder of mouse, dominant white spotting (W), results from mutations of the c-Kit protooncogene, which encodes and receptor for mast/stem cell growth factor. We identified a KIT gene mutation in a proband with classic autosomal dominant piebaldism. This mutation results in a Gly----Arg substitution at codon 664, within the tyrosine kinase domain. This substitution was not seen in any normal individuals and was completely linked to the piebald phenotype in the proband's family. Piebaldism in this family thus appears to be the human homologue to dominant white spotting (W) of the mouse.