Dominant negative and loss of function mutations of the c-kit (mast/stem cell growth factor receptor) proto-oncogene in human piebaldism.
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Spritz RA, Giebel LB, Holmes SA
Dominant negative and loss of function mutations of the c-kit (mast/stem cell growth factor receptor) proto-oncogene in human piebaldism.
Am J Hum Genet. 1992 Feb;50(2):261-9.
- PubMed ID
- 1370874 [ View in PubMed]
- Abstract
Piebaldism is an autosomal dominant disorder of melanocyte development and is characterized by congenital white patches of skin and hair from which melanocytes are completely absent. A similar disorder of the mouse, "dominant white spotting" (W), results from mutations of the c-kit proto-oncogene, which encodes the cellular tyrosine kinase receptor for the mast/stem cell growth factor. We have identified c-kit gene mutations in three patients with piebaldism. A missense substitution (Phe----Leu) at codon 584, within the tyrosine kinase domain, is associated with a severe piebald phenotype, whereas two different frameshifts, within codons 561 and 642, are both associated with a variable and relatively mild piebald phenotype. This is consistent with a possible "dominant negative" effect of missense c-kit polypeptides on the function of the dimeric receptor.