糖尿病的遗传学幻灯片.pptVIP

* MODY4 is caused by mutations in the insulin promoter factor-1 (IPF1; OMIM 600733) gene on chromosome 13q12.1. IPF1 is a pancreatic transcription factor that regulates expression of insulin, somatostatin and other genes. In addition, IPF1 is involved in the development of the pancreas. In adults, the expression of IPF1 is restricted to cells of the pancreas. Individuals with MODY4 mutations have decreased binding activity to the insulin gene promoter, which leads to reduced activation of the insulin gene in response to glucose. MODY4 mutations have also been associated with T2D. At least 6 genetic variants have been identified, including frameshift, insertions and missense mutations. They contribute to ~1% of all MODY cases. * Mutations in the hepatocyte nuclear factor 1-beta gene (HNF1B; OMIM 604284) on chromosome 17cen-q21.3 cause MODY5. This protein is also known as transcription factor 2 (TCF2). HNF1B is highly homologous to HNF1A (MODY3), and these genes likely interact to regulate gene expression. Individuals with MODY5 mutations have a lower renal threshold to glucose, which predisposes to severe renal disease. MODY5 mutations (including deletions, missense and nonsense mutations), are a rare cause of MODY and account for ~1% of all MODY cases, * The neurogenic differentiation factor 1 gene (NEUROD1; OMIM 601724) on chromosome 2q32 is MODY6. This gene is involved in the differentiation of neurons. It regulates insulin gene expression by binding to a critical motif on the insulin promotor. MODY6 mutations are a rare cause of MODY. Only a few genetic variants, including missense and nonsense mutations have been identified. * To summarize, all MODY genes are expressed in the islet cells of the pancreas, and play a role in the metabolism of glucose, the regulation of insulin or other genes involved in glucose transport, and / or the development of the fetal pancreas. Because MODY phenotypes vary depending on which MODY gene is involved, genetic t