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Beside the well\u2010known syndromes associated with an increased risk of adrenal phaeochromocytoma, Von Hippel Lindau disease, multiple endocrine neoplasia type 2 and neurofibromatosis type 1, the study of inherited predisposition to head and neck paragangliomas led to the discovery of the novel \u2018paraganglioma\u2013phaeochromocytoma syndrome\u2019 caused by germline mutations in three genes encoding subunits of the succinate dehydrogenase (SDH) enzyme (<jats:italic>SDHB<\/jats:italic>, <jats:italic>SDHC<\/jats:italic> and <jats:italic>SDHD<\/jats:italic>) thus opening an unexpected connection between mitochondrial tumour suppressor genes and neural crest\u2010derived cancers. Germline mutations in <jats:italic>SDH<\/jats:italic> genes are responsible for 6% and 9% of sporadic paragangliomas and phaeochromocytomas, respectively, 29% of paediatric cases, 38% of malignant tumours and more than 80% of familial aggregations of paraganglioma and phaeochromocytoma. The disease is characterized by autosomal dominant inheritance with a peculiar parent\u2010of\u2010origin effect for <jats:italic>SDHD<\/jats:italic> mutations. Life\u2010time tumour risk seems higher than 70% with variable clinical manifestantions depending on the mutated gene. In this review we summarize the most recent knowledge about the role of SDH deficiency in tumorigenesis, the spectrum and prevalence of <jats:italic>SDH<\/jats:italic> mutations derived from several series of cases, the related clinical manifestantions including rare phenotypes, such as the association of paragangliomas with gastrointestinal stromal tumours and kidney cancers, and the biological hypotheses attempting to explain genotype to phenotype correlation.<\/jats:p>","DOI":"10.1111\/j.1365-2796.2009.02111.x","type":"journal-article","created":{"date-parts":[[2009,4,7]],"date-time":"2009-04-07T04:43:59Z","timestamp":1239079439000},"page":"19-42","source":"Crossref","is-referenced-by-count":252,"title":["SDH mutations in tumorigenesis and inherited endocrine tumours: lesson from the phaeochromocytoma\u2013paraganglioma syndromes"],"prefix":"10.1111","volume":"266","author":[{"given":"B.","family":"Pasini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. 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