作者: Emanuela Leonardi , Maddalena Martella , Silvio C.E. Tosatto , Alessandra Murgia
DOI: 10.1111/J.1469-1809.2011.00647.X
关键词: Biology 、 Protein folding 、 Angiogenesis 、 Phenotype 、 Gene product 、 Disease 、 Cell growth 、 Molecular genetics 、 In silico 、 Genetics
摘要: Summary Mutational inactivation of the VHL gene is cause von Hippel-Lindau (VHL) disease, an autosomal dominant hereditary cancer syndrome predisposing to haemangioblastomas, pheochromocytomas and clear-cell renal carcinomas. The product (pVHL) functions as adapter in cellular processes including cell growth apoptosis. mutation analysis was carried out 426 unrelated subjects with phenotypes ranging from syndrome, isolated VHL-related tumours that could represent first manifestation disease. A total 111 individuals were found carry alterations, large deletions representing 40% variants. Eighteen 95 detected variants novel, seemingly disease-causing mutations; their pathogenic role has been evaluated silico for effects on protein folding interactions. Putative regions interaction between pVHL proteins involved common pathways have identified, assessing possible implications presence mutations these regions. All new predicted truncate or complete loss structure associated consistent type 1. Seven amino acid substitutions are mutations, one a neutral variant, whereas results two remain ambiguous. Our combined molecular approach evaluation putative contributes interpretation potential pathogenicity novel