Spritz R A, Giebel L B, Holmes S A
Department of Medical Genetics, University of Wisconsin, Madison.
Am J Hum Genet. 1992 Feb;50(2):261-9.
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.
斑驳病是一种常染色体显性黑素细胞发育障碍疾病，其特征为先天性皮肤和毛发白色斑块，这些部位完全没有黑素细胞。小鼠的一种类似疾病“显性白斑”（W）是由c-kit原癌基因突变引起的，该基因编码肥大细胞/干细胞生长因子的细胞酪氨酸激酶受体。我们在三名斑驳病患者中鉴定出了c-kit基因突变。酪氨酸激酶结构域内第584密码子处的错义替换（苯丙氨酸→亮氨酸）与严重的斑驳表型相关，而第561和642密码子内的两种不同移码突变均与可变且相对较轻的斑驳表型相关。这与错义c-kit多肽对二聚体受体功能可能产生的“显性负性”效应一致。
