Phenotype of SDHB mutation carriers in the Netherlands

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• 作者：Leonie T. van Hulsteijn (1)
  Nienke D. Niemeijer (1)
  Frederik J. Hes (2)
  Jean-Pierre Bayley (3)
  Carli M. Tops (2)
  Jeroen C. Jansen (4)
  Eleonora P. M. Corssmit (1)
  
• 关键词：SDHB mutation ; Phenotype ; Paragangliomas ; Pheochromocytomas
• 刊名：Familial Cancer
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：13
• 期：4
• 页码：651-657
• 全文大小：199 KB
• 参考文献：1. Amar L, Bertherat J, Baudin E et al (2005) Genetic testing in pheochromocytoma or functional paraganglioma. J Clin Oncol 23:8812-818 CrossRef
  2. Badenhop RF, Jansen JC, Fagan PA et al (2004) The prevalence of SDHB, SDHC, and SDHD mutations in patients with head and neck paraganglioma and association of mutations with clinical features. J Med Genet 41:e99 CrossRef
  3. Astuti D, Latif F, Dallol A et al (2001) Gene mutations in the succinate dehydrogenase subunit SDHB cause susceptibility to familial pheochromocytoma and to familial paraganglioma. Am J Hum Genet 69:49-4 CrossRef
  4. Baysal BE, Ferrell RE, Willett-Brozick JE et al (2000) Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma. Science 287:848-51 CrossRef
  5. Burnichon N, Briere JJ, Libe R et al (2010) SDHA is a tumor suppressor gene causing paraganglioma. Hum Mol Genet 19:3011-020 CrossRef
  6. Kunst HP, Rutten MH, de Monnink JP et al (2011) SDHAF2 (PGL2-SDH5) and hereditary head and neck paraganglioma. Clin Cancer Res 17:247-54 CrossRef
  7. Niemann S, Muller U (2000) Mutations in SDHC cause autosomal dominant paraganglioma, type 3. Nat Genet 26:268-70 CrossRef
  8. Comino-Mendez I, Gracia-Aznarez FJ, Schiavi F et al (2011) Exome sequencing identifies MAX mutations as a cause of hereditary pheochromocytoma. Nat Genet 43:663-67 CrossRef
  9. Qin Y, Yao L, King EE et al (2010) Germline mutations in TMEM127 confer susceptibility to pheochromocytoma. Nat Genet 42:229-33 CrossRef
  10. Benn DE, Gimenez-Roqueplo AP, Reilly JR et al (2006) Clinical presentation and penetrance of pheochromocytoma/paraganglioma syndromes. J Clin Endocrinol Metab 91:827-36 CrossRef
  11. Neumann HP, Pawlu C, Peczkowska M et al (2004) Distinct clinical features of paraganglioma syndromes associated with SDHB and SDHD gene mutations. JAMA 292:943-51 CrossRef
  12. Timmers HJ, Kozupa A, Eisenhofer G et al (2007) Clinical presentations, biochemical phenotypes, and genotype-phenotype correlations in patients with succinate dehydrogenase subunit B-associated pheochromocytomas and paragangliomas. J Clin Endocrinol Metab 92:779-86 CrossRef
  13. Burnichon N, Rohmer V, Amar L et al (2009) The succinate dehydrogenase genetic testing in a large prospective series of patients with paragangliomas. J Clin Endocrinol Metab 94:2817-827 CrossRef
  14. van Hulsteijn LT, Dekkers OM, Hes FJ, Smit JW, Corssmit EP (2012) Risk of malignant paraganglioma in SDHB-mutation and SDHD-mutation carriers: a systematic review and meta-analysis. J Med Genet 49:768-76 CrossRef
  15. Pasini B, Stratakis CA (2009) SDH mutations in tumorigenesis and inherited endocrine tumours: lesson from the phaeochromocytoma–paraganglioma syndromes. J Intern Med 266:19-2 CrossRef
  16. Bayley JP, Grimbergen AE, van Bunderen PA et al (2009) The first Dutch SDHB founder deletion in paraganglioma-pheochromocytoma patients. BMC Med Genet 10:34 CrossRef
  17. Hensen EF, van Duinen N, Jansen JC et al (2012) High prevalence of founder mutations of the succinate dehydrogenase g
• 作者单位：Leonie T. van Hulsteijn (1)
  Nienke D. Niemeijer (1)
  Frederik J. Hes (2)
  Jean-Pierre Bayley (3)
  Carli M. Tops (2)
  Jeroen C. Jansen (4)
  Eleonora P. M. Corssmit (1)
  
  1. Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands
  2. Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
  3. Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
  4. Department of Otorhinolargyngology, Leiden University Medical Center, Leiden, The Netherlands
  
• ISSN：1573-7292

文摘

SDHB mutation carriers are predisposed to developing paragangliomas (PGLs). The objective of this study was to assess genotype–phenotype correlations of a Dutch cohort of SDHB mutation carriers and assess potential differences in clinical phenotypes related to specific SDHB founder mutations. Forty-seven consecutive SDHB mutation carriers were included. Initial screening consisted of measurement of 24?h urinary excretion of catecholamines and their metabolites in duplicate, repeated annually if initial biochemical screening was negative. Whole-body imaging studies with magnetic resonance imaging (MRI) or computed tomography (CT) and/or 123I-MIBG scintigraphy were performed in case of catecholamine excess, and MRI or CT scans of thorax, abdomen and pelvis were performed every 2?years regardless of catecholamine levels. Repetitive head-and-neck MRI was performed at 2?year intervals. Mean follow-up was 3.6?±?3.6?years. Twenty-seven persons (57?%) carried the SDHB c.423+1 G>A mutation and seven persons (15?%) the SDHB c.201-4429_287-933del (exon 3 deletion) mutation. No differences were found in the clinical phenotype of carriers of these two specific SDHB mutations. By end of follow-up, 49?% of SDHB mutation carriers displayed no biochemical or radiological evidence of manifest disease, i.e. they were unaffected carriers. Three persons (6?%) had been diagnosed with a pheochromocytoma (PCC), four with a sympathetic PGL (sPGL) (9?%), 18 with a HNPGL (38?%), and two persons (4?%) had developed a malignant paraganglioma, i.e. metastatic disease. In conclusion, the two main Dutch SDHB founder mutations do not differ in clinical expression and result in a relatively mild phenotype. Over one-third of SDHB mutation carriers develop HNPGL, with sPGL/PCC in only 15?% and malignancy in only 4?%.