RESUMO
Hirschsprung disease (HSCR, aganglionic megacolon) represents the main genetic cause of functional intestinal obstruction with an incidence of 1/5000 live births. This developmental disorder is a neurocristopathy and is characterised by the absence of the enteric ganglia along a variable length of the intestine. In the last decades, the development of surgical approaches has importantly decreased mortality and morbidity which allowed the emergence of familial cases. Isolated HSCR appears to be a non-Mendelian malformation with low, sex-dependent penetrance, and variable expression according to the length of the aganglionic segment. While all Mendelian modes of inheritance have been described in syndromic HSCR, isolated HSCR stands as a model for genetic disorders with complex patterns of inheritance. The tyrosine kinase receptor RET is the major gene with both rare coding sequence mutations and/or a frequent variant located in an enhancer element predisposing to the disease. Hitherto, 10 genes and five loci have been found to be involved in HSCR development.
Assuntos
Doença de Hirschsprung/genética , Doença de Hirschsprung/patologia , Aberrações Cromossômicas , Feminino , Doença de Hirschsprung/epidemiologia , Humanos , Obstrução Intestinal/genética , Masculino , Biologia Molecular , Mutação , Receptores Proteína Tirosina Quinases/genética , SíndromeAssuntos
Variação Genética , Animais , Ligação Genética , Haplótipos , Doença de Hirschsprung , Humanos , Camundongos , Modelos Genéticos , Mutação , Proteínas Oncogênicas/genética , Fenótipo , Proteínas Proto-Oncogênicas c-ret , Receptores Proteína Tirosina Quinases/genética , Receptor de Endotelina B/genética , Especificidade da EspécieRESUMO
The c-myc gene and the expression of the c-Myc protein are frequently altered in human cancers. The c-myc gene encodes the transcription factor c-Myc, which heterodimerizes with a partner protein, termed Max, to regulate gene expression. Max also heterodimerizes with the Mad family of proteins to repress transcription, antagonize c-Myc, and promote cellular differentiation. The constitutive activation of c-myc expression is key to the genesis of many cancers, and hence the understanding of c-Myc function depends on our understanding of its target genes. In this review, we attempt to place the putative target genes of c-Myc in the context of c-Myc-mediated phenotypes. From this perspective, c-Myc emerges as an oncogenic transcription factor that integrates the cell cycle machinery with cell adhesion, cellular metabolism, and the apoptotic pathways.
