A novel mutation in the c-KIT protooncogene in a family with piebaldism
- Univ. of Milan (Italy)
Human piebaldism is a dominant disorder (MIN No. 17289) caused by impaired migration of melanoblasts from the neural crest to the epidermis during embryonic development. Mutations in the c-KIT gene which encodes the tyrosinkinase (TK) receptor of SCF have been causally related to the disease. Significantly six out of the seven point mutations so far reported in piebaldic patients are clustered in the I{degrees} TK domain of the gene. We studied an Italian family in which the piebald trait had been transmitted through at least six generations, which includes 39 affected and 1 healthy member, and sequencing of the I{degrees} TK domain exons failed to reveal any alteration in this critical region. Conversely, exon 19 in the II{degrees} TK domain showed an SSCP pattern which differed in the piebaldic from healthy family members and controls. Direct sequencing of exon 19 showed a 12 base deletion (AACACGCACCTG) leading the lack of 4 amino acids (gln, his, ala, pro) in the receptor protein. This is the first mutation in the II{degrees} TK domain of the c-KIT gene. Like point mutations in the I{degrees} TK domain, it causes a full clinical phenotype, whereas frameshift and whole gene mutations underlie a mild phenotype. Sequence analysis evidenced a direct repeat motif (CTG) at both deletion junctions and deletion 3{prime} end. This suggests that a {open_quotes}slipped mispairing{close_quotes} mechanism at DNA replication may be involved in the deletion.
- OSTI ID:
- 134242
- Report Number(s):
- CONF-941009-; ISSN 0002-9297; TRN: 95:005313-0978
- Journal Information:
- American Journal of Human Genetics, Vol. 55, Issue Suppl.3; Conference: 44. annual meeting of the American Society of Human Genetics, Montreal (Canada), 18-22 Oct 1994; Other Information: PBD: Sep 1994
- Country of Publication:
- United States
- Language:
- English
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