Identification of three new variants of SDHx genes in a cohort of Portuguese patients with extra-adrenal paragangliomas

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• 作者：R. Domingues ; P. Montalv茫o ; M. Magalh茫es…
• 关键词：Familial syndromes ; germline mutations ; hereditary diseases ; paraganglioma ; SDHx genes
• 刊名：Journal of Endocrinological Investigation
• 出版年：2012
• 出版时间：December 2012
• 年：2012
• 卷：35
• 期：11
• 页码：975-980
• 全文大小：
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• 作者单位：R. Domingues (1)
  P. Montalv茫o (2)
  M. Magalh茫es (2)
  R. Santos (3)
  L. Duarte (4)
  M. J. Bugalho MD, PhD (1) (3) (5)
  
  1. Centro de Investiga莽茫o de Patobiologia Molecular (CIPM), Instituto Portugu锚s de Oncologia de Lisboa Francisco Gentil E.P.E., Lisbon, Portugal
  2. Servi莽o de Otorrinolaringologia, Instituto Portugu锚s de Oncologia de Lisboa Francisco Gentil E.P.E., Lisbon, Portugal
  3. Servi莽o de Endocrinologia, Instituto Portugu锚s de Oncologia de Lisboa Francisco Gentil E.P.E., Rua Professor Lima Basto, 1099-023, Lisboa, Portugal
  4. Servi莽o de Endocrinologia, Hospital Curry Cabral, Lisbon, Portugal
  5. Cl铆nica Universit谩ria de Endocrinologia, Faculdade de Ci锚ncias M茅dicas (FCM), Universidade Nova de Lisboa, Lisbon, Portugal
  
• 刊物类别：Medicine/Public Health, general; Endocrinology; Metabolic Diseases;
• 刊物主题：Medicine/Public Health, general; Endocrinology; Metabolic Diseases;
• 出版者：Springer International Publishing
• ISSN：1720-8386

文摘

Background: Extra-adrenal paragangliomas (PGL) are rare neoplasms occurring in sporadic and familial forms, the latter mostly in association with germline mutations of SDHB, SDHC or SDHD genes. Aim: Characterize frequency and spectrum of germline mutations among a cohort of Portuguese patients with extra-adrenal PGL. Design: Molecular and clinical data were reviewed on 44 patients referred for genetic testing by a single laboratory. Results: Genetic analysis identified 11 patients with head and neck PGL (30.6%) positive for SDHx gene mutations (6 SDHD, 4 SDHB, 1 SDHC) and 4 patients with abdominal or pelvic PGL (50%) positive for SDHx gene mutations (4 SDHB). Large deletions made up about 20% of the mutations detected. Mutation carriers were younger and more frequently had multiple or malignant PGL than patients without mutations. Only 11 % of the head and neck PGL were secretory. In contrast, 100% of the abdominal or pelvic PGL were secretory. Five patients had a malignant PGL (4 SDHB, 1 apparently sporadic). Three novel mutations were identified: two in the SDHD gene (c.411delT [p.Leu139PhefsX29] and c.371_390del20insGG [p.Ala124_Ala130delinsGly]), one in the SDHB gene (c.49A>G [p.Thr17Ala]). The SDHD variant c.411 delT [p.Leu139PhefsX29] was present in 3 apparently unrelated patients. Molecular genetic testing of 22 relatives disclosed 16 mutation carriers. Conclusions: Genetic analysis identified 15 patients (34.1%) and 16 at-risk individuals (72.7%) positive for SDHx gene mutations. The finding of three novel mutations broadens the mutational profile of the mitochondrial complex II succinate dehydrogenase genes reported in other large European series of patients with paragangliomas. Further studies are needed to clarify whether the high frequency of the SDHD variant c.411 delT [p.Leu139PhefsX29] corresponds to a founder mutation. Key-words Familial syndromes germline mutations hereditary diseases paraganglioma SDHx genes