Deletion of the SLUG (SNAI2) gene results in human piebaldism

Slug is a zinc‐finger neural crest transcription factor, encoded by the SLUG gene, which is critical for development of hematopoietic stem cells, germ cells, and melanoblasts in the mouse. In mouse, heterozygous and homozygous slug mutations result in anemia, infertility, white forehead blaze, and depigmentation of the ventral body, tail, and feet. This phenotype is very similar to the heterozygous W (KIT)‐mutant mouse phenotype and to human piebaldism, which is characterized by a congenital depigmented patches and poliosis (white forelock). To investigate the possibility that some cases of human piebaldism might result from abnormalities of the human SLUG (SNAI2) gene, we carried out Southern blot analysis of the SLUG gene in 17 unrelated patients with piebaldism, who lack apparent KIT mutations. Three of these patients had evident heterozygous deletions of the SLUG gene encompassing the entire coding region. Real‐time PCR confirmed the deletion in all cases. Fluoresence in situ hybridization (FISH) of genomic SLUG probes to metaphase chromosomes independently confirmed the deletion in one of the cases. These findings indicate that some cases of human piebaldism result from mutation of the SLUG gene on chromosome 8, and provide further strong evidence for the role of SLUG in the development of human melanocytes. © 2003 Wiley‐Liss, Inc.