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 00:00:00 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), Vol. 50:2; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

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