Analysis of KIT, SCF, and Initial Screening of SLUG in Patients with Piebaldism.

摘要

Piebaldism is an autosomal dominant disorder, characterized by congenital leukoderma typically on the abdomen, knees, and forehead. Mice models for human piebaldism are the W dominant white spotting, the steel mice and the mice that are mutated for the slug gene. Human genes for these mice models were investigated in this study. Genomic DNAs of peripheral leukocytes were prepared from twenty-two patients with piebaldism. PCR-direct sequencing or screening by SSCP and subsequent sequencing of all of the exons and flanking introns of KIT, SCF (stem cell factor), and SLUG genes disclosed six pathological mutations only in KIT. Among them five were novel: 358delG, IVS3-2A>G, Q346X, H650L, and D792Y. His650 is located in the strand connecting the helix alphaC and the downstream beta-sheet of the N-lobe of the active KIT kinase domain, the crystal fine structure of which was determined recently. Asp792 is situated in the center of the kinase active site of interdomain cleft between the N-lobe and the C-lobe.No pathological mutations were found in SCF or SLUG in our screening system. Analysis of mutations in the KIT kinase domain may offer an insight into the detailed functional role of this fascinating protein.