Sánchez-Martín Manuel, Pérez-Losada Jesús, Rodríguez-García Arancha, González-Sánchez Belén, Korf Bruce R, Kuster W, Moss Celia, Spritz Richard A, Sánchez-García I
Instituto de Biología Molecular y Celular del Cáncer (IBMCC), Centro de Investigación del Cáncer, CSIC/Universidad de Salamanca, Salamanca, Spain.
Am J Med Genet A. 2003 Oct 1;122A(2):125-32. doi: 10.1002/ajmg.a.20345.
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.
Slug是一种锌指神经嵴转录因子，由SLUG基因编码，对小鼠造血干细胞、生殖细胞和黑素母细胞的发育至关重要。在小鼠中，杂合和纯合的slug突变会导致贫血、不育、前额白斑以及腹部、尾巴和足部色素脱失。这种表型与杂合W（KIT）突变小鼠的表型以及人类斑驳病非常相似，后者的特征是先天性色素脱失斑和白发症（白色额发）。为了研究人类斑驳病的某些病例可能是由人类SLUG（SNAI2）基因异常引起的可能性，我们对17名无明显KIT突变的无关斑驳病患者的SLUG基因进行了Southern印迹分析。其中三名患者存在明显的SLUG基因杂合缺失，缺失区域包括整个编码区。实时PCR在所有病例中均证实了这种缺失。用基因组SLUG探针与中期染色体进行荧光原位杂交（FISH）在其中一例中独立证实了这种缺失。这些发现表明，人类斑驳病的某些病例是由8号染色体上的SLUG基因突变引起的，并为SLUG在人类黑素细胞发育中的作用提供了进一步的确凿证据。
