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

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-o...

Full description

Saved in:
Bibliographic Details
Published in:American journal of human genetics 1992-02, Vol.50 (2), p.261-269
Main Authors: SPRITZ, R. A, GIEBEL, L. B, HOLMES, S. A
Format: Article
Language:English
Subjects:
Amino Acid Sequence
ANIMAL CELLS
Base Sequence
BASIC BIOLOGICAL SCIENCES
Biological and medical sciences
Blotting, Southern
BODY
c-Kit
CODONS
CONNECTIVE TISSUE CELLS
Dermatology
DISEASES
DOMINANT MUTATIONS
ENZYMES
ETIOLOGY
Female
GENE MUTATIONS
GENES
Genes, Dominant
Genetic Linkage
GROWTH FACTORS
HEREDITARY DISEASES
Hereditary diseases of the skin. Congenital diseases of the skin. Haemangioma of the skin, of mucosae and of soft tissue
Heterozygote
Humans
HYDROXY COMPOUNDS
HYDROXYLASES
Male
MAST CELLS
mast/stem cell growth factor
Medical sciences
MELANIN
MEMBRANE PROTEINS
MITOGENS
Molecular Sequence Data
Mutation
MUTATIONS
ONCOGENES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
OXIDOREDUCTASES
PATIENTS
Pedigree
PHENOTYPE
Piebaldism - genetics
PIGMENTS
Polymerase Chain Reaction
Polymorphism, Genetic
PROTEINS
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins c-kit
Proto-Oncogenes
RECEPTORS
SKIN
SKIN DISEASES
SOMATIC CELLS 550200 > Biochemistry
STEM CELLS
TYROSINASE
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0002-9297
1537-6605