Dominant negative and loss of function mutations of the c-kit (mast/stem cell growth factor receptor) proto-oncogene in human piebaldism

Journal Article · Sat Feb 01 04:00:00 EST 1992 · American Journal of Human Genetics; (United States)

OSTI ID:6913933

Spritz, R A; Giebel, L B; Holmes, S A ^[1]

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1. University of Wisconsin, Madison (United States)

Piebaldism is an autosomal dominant disorder of melanocyte development and is characterized by congenital white parches 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 kinases receptor for the mast/stem cell growth factor. The authors have identified c-kit gene mutations in three patients with piebaldism. A missense substitution (Phe[r arrow]Leu) at codon 584, within the tyrosine kinases 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.

• OSTI ID: 6913933
• Journal Information: American Journal of Human Genetics; (United States), Journal Name: American Journal of Human Genetics; (United States) Vol. 50:2; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

550200* -- Biochemistry
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
BODY
CODONS
CONNECTIVE TISSUE CELLS
DISEASES
DOMINANT MUTATIONS
ENZYMES
ETIOLOGY
GENE MUTATIONS
GENES
GROWTH FACTORS
HEREDITARY DISEASES
HYDROXY COMPOUNDS
HYDROXYLASES
MAST CELLS
MELANIN
MEMBRANE PROTEINS
MITOGENS
MUTATIONS
ONCOGENES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
OXIDOREDUCTASES
PATIENTS
PHENOTYPE
PIGMENTS
PROTEINS
RECEPTORS
SKIN
SKIN DISEASES
SOMATIC CELLS
STEM CELLS
TYROSINASE