Dentification Of Novel KIT Gene Mutation In A Chinese Han Pedigree With Piebaldism

Background Piebaldism (OMIM 164920) is a rare autosomal dominant inherited skin disorder characterized by congenital white patches in skin and hair with complete absence of melanocytes, typically on the forehead, chest, abdomen and extremities. The leukoderma is usually stable throughout life, although pigmented macules may develop at the margins and even within the white macules. Piebaldism may be associated with a genetic heterogeneity. Until now, the mutations responsible for piebaldism have been identified in the KIT gene on chromosome 4q12 or in the SLUG gene on chromosome 8. The KIT gene mutations can be found in 75% patients with piebaldism. KIT gene encodes the cell surface transmembrane tyrosine kinase (TK) receptor for mast/stem cell growth factor, which is a critical factor for melanoblast migration, proliferation, differentiation and survival. To date, more than 40 mutations of KIT gene have been identified in patients with piebaldism. There is a relationship between genotype and phenotype in piebaldism.Objective To search for KIT gene mutations in Chinese Han patients with piebaldism, summarize clinical features of Chinese Han piebaldism patients and confirm the genotype-phenotype correlation reported in Western population.Methods (1) All 21 exons including intron-exon boundaries were amplified by polymerase chain reaction (PCR) using published primers, then we sequenced the KIT gene in a Chinese Han pedigree with 2 piebaldism patients. (2) We searched for case reports and papers about piebaldism since 1989 by Chinese Biology Medicine (CBM) disc and Pubmed. The clinical features and mutation analysis of piebaldism in China were summarized. Meanwhile, we confirmed the genotype-phenotype correlation in piebaldism patients, compared with the results in Western population.Results (1) A novel missense mutation was found in these two patients with piebaldism, which was c.172T→G (G58Y). The mutation was not found in the healthy members of family and in 100 unrelated controls. (2) We presented the clinical and genetic features of piebaldism by reviewing the cases reported in China. It confirmed the relationship between genotype and phenotype founded in the Western population.Conclusion Here we report a Chinese Han family with piebaldism with a novel missense mutation (c.172T→G (G58Y)) in KIT gene. This mutation may be the underlying causes of piebaldism pedigree in our study, not common polymorphism. Our literature review indicates that piebaldism is not very uncommon in China and adds new data to the worldwide knowledge of genotype-phenotype correlation in piebaldism.