Deletion of the c-kit protooncogene in the human developmental defect piebald trait
- Univ. of Texas, Dallas (United States)
- Genelabs, Inc., Redwood City, CA (United States)
The protooncogene c-kit is critical for development of hematopoietic stem cells, germ cells, and melanoblasts in the mouse. Homozygous mutations of this gene in the mouse cause anemia, infertility, and albinism, whereas heterozygous mutant mice usually exhibit only a white forehead blaze and depigmentation of the ventral body, tail, and feet. The heterozygous mouse phenotype is very similar to human piebald trait, which is characterized by a congenital white hair forelock and ventral and extremity depigmentation. To investigate the possibility that alterations in the human c-kit gene may be a cause of piebald trait, DNA from seven unrelated affected individuals was examined by Southern blot analysis. One subject, although cytogenetically normal, has a heterozygous deletion of the c-kit protooncogene. This deletion encompasses the entire coding region for c-kit and also involves the closely linked gene for platelet-derived growth factor receptor {alpha}. These findings provide molecular evidence mapping piebald trait to the c-kit locus on chromosome 4. Although the authors cannot exclude the involvement of other closely linked genes, the demonstration of a genomic c-kit deletion in one subject with piebald trait and the marked concordance of the human and mouse phenotypes provide strong evidence for the role of c-kit in the development of human melanocytes and in the pathogenesis of piebald trait.
- OSTI ID:
- 5602672
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America; (United States), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (United States) Vol. 88:23; ISSN PNASA; ISSN 0027-8424
- Country of Publication:
- United States
- Language:
- English
Similar Records
A novel mutation in the c-KIT protooncogene in a family with piebaldism
Dominant negative and loss of function mutations of the c-kit (mast/stem cell growth factor receptor) proto-oncogene in human piebaldism
Related Subjects
59 BASIC BIOLOGICAL SCIENCES
AUTORADIOGRAPHY
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BLOOD PLATELETS
BODY FLUIDS
CHROMOSOMAL ABERRATIONS
CHROMOSOMES
DISEASES
DNA
DNA HYBRIDIZATION
ETIOLOGY
GENES
GENETIC MAPPING
GROWTH FACTORS
HEREDITARY DISEASES
HETEROCHROMOSOMES
HYBRIDIZATION
MAPPING
MATERIALS
MELANOMAS
MEMBRANE PROTEINS
MITOGENS
MUTATIONS
NEOPLASMS
NUCLEIC ACIDS
ONCOGENES
ORGANIC COMPOUNDS
PIGMENTS
PROTEINS
RECEPTORS