Logo of ajhgLink to Publisher's site
Am J Hum Genet. 1995 Jan; 56(1): 58–66.
PMCID: PMC1801299

Novel Mutations and Deletions of the KIT (Steel Factor Receptor) Gene in Human Piebaldism


Piebaldism is an autosomal dominant genetic disorder of pigmentation characterized by white patches of skin and hair. Melanocytes are lacking in these hypopigmented regions, the result of mutations of the KIT gene, which encodes the cell surface receptor for steel factor (SLF). We describe the analysis of 26 unrelated patients with piebaldism-like hypopigmentation—17 typical patients, 5 with atypical clinical features or family histories, and 4 with other disorders that involve white spotting. We identified novel pathologic mutations or deletions of the KIT gene in 10 (59%) of the typical patients, and in 2 (40%) of the atypical patients. Overall, we have identified pathologic KIT gene mutations in 21 (75%) of 28 unrelated patients with typical piebaldism we have studied. Of the patients without apparent KIT mutations, none have apparent abnormalities of the gene encoding SLF itself (MGF), and genetic linkage analyses in two of these families are suggestive of linkage of the piebald phenotype to KIT. Thus, most patients with typical piebaldism appear to have abnormalities of the KIT gene.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.6M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Barton DE, Kwon BS, Francke U. Human tyrosinase gene, mapped to chromosome 11 (q14----q21), defines second region of homology with mouse chromosome 7. Genomics. 1988 Jul;3(1):17–24. [PubMed]
  • Chabot B, Stephenson DA, Chapman VM, Besmer P, Bernstein A. The proto-oncogene c-kit encoding a transmembrane tyrosine kinase receptor maps to the mouse W locus. Nature. 1988 Sep 1;335(6185):88–89. [PubMed]
  • Fleischman RA. Human piebald trait resulting from a dominant negative mutant allele of the c-kit membrane receptor gene. J Clin Invest. 1992 Jun;89(6):1713–1717. [PMC free article] [PubMed]
  • Fleischman RA, Saltman DL, Stastny V, Zneimer S. Deletion of the c-kit protooncogene in the human developmental defect piebald trait. Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10885–10889. [PMC free article] [PubMed]
  • Gatto M, Giannaula R, Micheli F. Piebaldismo asociado a cáncer. Med Cutan Ibero Lat Am. 1985;13(6):545–556. [PubMed]
  • Geissler EN, Ryan MA, Housman DE. The dominant-white spotting (W) locus of the mouse encodes the c-kit proto-oncogene. Cell. 1988 Oct 7;55(1):185–192. [PubMed]
  • Giebel LB, Spritz RA. Mutation of the KIT (mast/stem cell growth factor receptor) protooncogene in human piebaldism. Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8696–8699. [PMC free article] [PubMed]
  • Giebel LB, Strunk KM, Holmes SA, Spritz RA. Organization and nucleotide sequence of the human KIT (mast/stem cell growth factor receptor) proto-oncogene. Oncogene. 1992 Nov;7(11):2207–2217. [PubMed]
  • Kaplan P, de Chaderévian JP. Piebaldism-Waardenburg syndrome: histopathologic evidence for a neural crest syndrome. Am J Med Genet. 1988 Nov;31(3):679–688. [PubMed]
  • Martin FH, Suggs SV, Langley KE, Lu HS, Ting J, Okino KH, Morris CF, McNiece IK, Jacobsen FW, Mendiaz EA, et al. Primary structure and functional expression of rat and human stem cell factor DNAs. Cell. 1990 Oct 5;63(1):203–211. [PubMed]
  • Nishikawa S, Kusakabe M, Yoshinaga K, Ogawa M, Hayashi S, Kunisada T, Era T, Sakakura T, Nishikawa S. In utero manipulation of coat color formation by a monoclonal anti-c-kit antibody: two distinct waves of c-kit-dependency during melanocyte development. EMBO J. 1991 Aug;10(8):2111–2118. [PMC free article] [PubMed]
  • Nocka K, Tan JC, Chiu E, Chu TY, Ray P, Traktman P, Besmer P. Molecular bases of dominant negative and loss of function mutations at the murine c-kit/white spotting locus: W37, Wv, W41 and W. EMBO J. 1990 Jun;9(6):1805–1813. [PMC free article] [PubMed]
  • Ott J. Estimation of the recombination fraction in human pedigrees: efficient computation of the likelihood for human linkage studies. Am J Hum Genet. 1974 Sep;26(5):588–597. [PMC free article] [PubMed]
  • Poduslo SE, Dean M, Kolch U, O'Brien SJ. Detecting high-resolution polymorphisms in human coding loci by combining PCR and single-strand conformation polymorphism (SSCP) analysis. Am J Hum Genet. 1991 Jul;49(1):106–111. [PMC free article] [PubMed]
  • Saiki RK, Gelfand DH, Stoffel S, Scharf SJ, Higuchi R, Horn GT, Mullis KB, Erlich HA. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. [PubMed]
  • Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. [PMC free article] [PubMed]
  • Southern EM. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. [PubMed]
  • Spritz RA, Droetto S, Fukushima Y. Deletion of the KIT and PDGFRA genes in a patient with piebaldism. Am J Med Genet. 1992 Nov 1;44(4):492–495. [PubMed]
  • Spritz RA, Giebel LB, Holmes SA. Dominant negative and loss of function mutations of the c-kit (mast/stem cell growth factor receptor) proto-oncogene in human piebaldism. Am J Hum Genet. 1992 Feb;50(2):261–269. [PMC free article] [PubMed]
  • Spritz RA, Holmes SA. Polymerase chain reaction detection of a novel human KIT (mast/stem cell growth factor receptor) gene polymorphism by single-strand conformation polymorphism analysis or by SmaI or BstNI cleavage. Hum Genet. 1993 Sep;92(2):208–209. [PubMed]
  • Spritz RA, Holmes SA, Berg SZ, Nordlund JJ, Fukai K. A recurrent deletion in the KIT (mast/stem cell growth factor receptor) proto-oncogene is a frequent cause of human piebaldism. Hum Mol Genet. 1993 Sep;2(9):1499–1500. [PubMed]
  • Spritz RA, Holmes SA, Itin P, Küster W. Novel mutations of the KIT (mast/stem cell growth factor receptor) proto-oncogene in human piebaldism. J Invest Dermatol. 1993 Jul;101(1):22–25. [PubMed]
  • Spritz RA, Holmes SA, Ramesar R, Greenberg J, Curtis D, Beighton P. Mutations of the KIT (mast/stem cell growth factor receptor) proto-oncogene account for a continuous range of phenotypes in human piebaldism. Am J Hum Genet. 1992 Nov;51(5):1058–1065. [PMC free article] [PubMed]
  • Spritz RA, Ho L, Strunk KM. Inhibition of proliferation of human melanocytes by a KIT antisense oligodeoxynucleotide: implications for human piebaldism and mouse dominant white spotting (W). J Invest Dermatol. 1994 Aug;103(2):148–150. [PubMed]
  • Spritz RA, Strunk KM, Lee ST, Lu-Kuo JM, Ward DC, Le Paslier D, Altherr MR, Dorman TE, Moir DT. A YAC contig spanning a cluster of human type III receptor protein tyrosine kinase genes (PDGFRA-KIT-KDR) in chromosome segment 4q12. Genomics. 1994 Jul 15;22(2):431–436. [PubMed]
  • Stephenson DA, Mercola M, Anderson E, Wang CY, Stiles CD, Bowen-Pope DF, Chapman VM. Platelet-derived growth factor receptor alpha-subunit gene (Pdgfra) is deleted in the mouse patch (Ph) mutation. Proc Natl Acad Sci U S A. 1991 Jan 1;88(1):6–10. [PMC free article] [PubMed]
  • Tsujimura T, Hirota S, Nomura S, Niwa Y, Yamazaki M, Tono T, Morii E, Kim HM, Kondo K, Nishimune Y, et al. Characterization of Ws mutant allele of rats: a 12-base deletion in tyrosine kinase domain of c-kit gene. Blood. 1991 Oct 15;78(8):1942–1946. [PubMed]
  • Yarden Y, Kuang WJ, Yang-Feng T, Coussens L, Munemitsu S, Dull TJ, Chen E, Schlessinger J, Francke U, Ullrich A. Human proto-oncogene c-kit: a new cell surface receptor tyrosine kinase for an unidentified ligand. EMBO J. 1987 Nov;6(11):3341–3351. [PMC free article] [PubMed]

Articles from American Journal of Human Genetics are provided here courtesy of American Society of Human Genetics


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...