Deletion of the c-kit protooncogene in the human developmental defect piebald trait

Roger A. Fleischman, David L. Saltman, Victor Stastny, Susan Zneimer

Research output: Contribution to journalArticlepeer-review

189 Scopus citations

Abstract

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 α. Fluorescence in situ hybridization of genomic c-kit probes to metaphase chromosomes independently confirmed the deletion in this case. These findings provide molecular evidence mapping piebald trait to the c-kit locus on chromosome 4. Although we 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.

Original languageEnglish
Pages (from-to)10885-10889
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume88
Issue number23
StatePublished - 1991

Keywords

  • Chromosome deletion
  • Melanocytes
  • Melanoma growth-stimulatory activity
  • Pigmentation disorders
  • Platelet-derived growth factor receptor α

ASJC Scopus subject areas

  • General

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