NOVEL MUTATIONS AND DELETIONS OF THE KIT (STEEL FACTOR-RECEPTOR) GENEIN HUMAN PIEBALDISM

Piebaldism is an autosomal dominant genetic disorder of pigmentation c haracterized by white patches of skin and hair. Melanocytes are lackin g in these hypopigmented regions, the result of mutations of the KIT g ene, which encodes the cell surface receptor for steel factor (SLF). W e describe the analysis of 26 unrelated patients with piebaldism-like hypopigmentation-17 typical patients, 5 with atypical clinical feature s or family histories, and 4 with other disorders that involve white s potting. We identified novel pathologic mutations or deletions of the KIT gene in 10 (59%) of the typical patients, and in 2 (40%) of the at ypical patients. Overall, we have identified pathologic KIT gene mutat ions in 21 (75%) of 28 unrelated patients with typical piebaldism we h ave studied. Of the patients without apparent KIT mutations, none have apparent abnormalities of the gene encoding SLF itself (MGF), and gen etic linkage analyses in two of these families are suggestive of linka ge of the piebald phenotype to KIT. Thus, most patients with typical p iebaldism appear to have abnormalities of the KIT gene.