Mutation of the KIT (Mast/Stem Cell Growth Factor Receptor) Protooncogene in Human Piebaldism

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 88; no. 19; pp. 8696 - 8699
• Main Authors: Giebel, Lutz B., Spritz, Richard A.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 01.10.1991; National Acad Sciences
• Subjects: 550200 - Biochemistry; Amino Acid Sequence; AMINO ACIDS; ARGININE; Base Sequence; BASIC BIOLOGICAL SCIENCES; BODY; CARBOXYLIC ACIDS; Codons; Complementary DNA; DISEASES; DNA; DNA Mutational Analysis; DNA SEQUENCING; DOMINANT MUTATIONS; ENZYMES; ETIOLOGY; Exons; GENE AMPLIFICATION; GENE MUTATIONS; GENES; Genes, Dominant; Genetic Linkage; Genetic mutation; GLYCINE; HAIR; HEREDITARY DISEASES; Humans; mast/stem cell growth factor; Molecular Sequence Data; MUTATIONS; Nucleotide sequences; Oligonucleotides - chemistry; ONCOGENES; ORGANIC ACIDS; ORGANIC COMPOUNDS; ORGANS; Pedigree; PHOSPHORUS-GROUP TRANSFERASES; PHOSPHOTRANSFERASES; Piebaldism; Piebaldism - genetics; PIGMENTS; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Protein-Tyrosine Kinases - genetics; PROTEINS; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins c-kit; Proto-Oncogenes; Receptors; Receptors, Cell Surface - genetics; SKIN; STRUCTURAL CHEMICAL ANALYSIS; TRANSFERASES
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.88.19.8696

Piebaldism is an autosomal dominant genetic disorder characterized by congenital 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 the 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.