Paraganglioma Syndrome

Abstract:  Paraganglioma syndrome includes head and neck paraganglioma and pheochromocytoma, and is classified according to the three susceptibility genes involved, SDHB, SDHC, and SDHD. This study assessed the prevalence of germline mutations in SDHB, SDHC, and SDHD genes in a consecutive population admitted to Padova Hospital consisting of 20 patients with head and neck paraganglioma (HNP). Mutations were identified in the three genes in four affected individuals, three sporadic cases and one with family history of HNP. The novel SDHB p.R242C mutation was identified in a sporadic monolateral carotid body tumor. The SDHC p.Q147X mutation, the first to be described in Italy, was detected in a sporadic monolateral jugulotympanic paraganglioma. The SDHD p.Y114C mutation was identified in two unrelated patients, one familial case of bilateral carotid body tumor and one multiple paraganglioma. SDHB, SDHC, and SDHD molecular screening is important in all HNPs, with or without primary indicators of paraganglioma syndrome, to orient mutation‐driven clinical screening for additional HNPs and pheochromocytoma.

[1]  B. Devlin,et al.  Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma. , 2000, Science.

[2]  L. Feng,et al.  SDHB, SDHC, and SDHD mutation screen in sporadic and familial head and neck paragangliomas , 2004, Clinical genetics.

[3]  M. James,et al.  Fine mapping of an imprinted gene for familial nonchromaffin paragangliomas, on chromosome 11q23. , 1997, American journal of human genetics.

[4]  B. Baysal.  Hereditary paraganglioma targets diverse paraganglia , 2002, Journal of medical genetics.

[5]  P. Devilee,et al.  Nearly all hereditary paragangliomas in The Netherlands are caused by two founder mutations in the SDHD gene , 2001, Genes, chromosomes & cancer.

[6]  M. Gillman,et al.  Familial carotid body tumors: Case report and epidemiologic review , 1980, Cancer.

[7]  E S Husebye,et al.  Gene mutations in the succinate dehydrogenase subunit SDHB cause susceptibility to familial pheochromocytoma and to familial paraganglioma. , 2001, American journal of human genetics.

[8]  W. Rubinstein,et al.  Prevalence of SDHB, SDHC, and SDHD germline mutations in clinic patients with head and neck paragangliomas , 2002, Journal of medical genetics.

[9]  Ulrich Müller,et al.  Mutations in SDHC cause autosomal dominant paraganglioma, type 3 , 2000, Nature Genetics.

[10]  J. Milunsky,et al.  Novel mutations and the emergence of a common mutation in the SDHD gene causing familial paraganglioma. , 2001, American journal of medical genetics.

[11]  M. Mascalchi,et al.  Phenotype variability of neural crest derived tumours in six Italian families segregating the same founder SDHD mutation Q109X , 2005, Journal of Medical Genetics.

[12]  X. Matías-Guiu,et al.  Mutation Analysis of the SDHD Gene in Four Kindreds with Familial Paraganglioma: Description of One Novel Germline Mutation , 2005, Diagnostic molecular pathology : the American journal of surgical pathology, part B.

[13]  B. Baysal.  Genomic imprinting and environment in hereditary paraganglioma , 2004, American journal of medical genetics. Part C, Seminars in medical genetics.

[14]  E. Mariman,et al.  Analysis of a second family with hereditary non-chromaffin paragangliomas locates the underlying gene at the proximal region of chromosome 11q , 1993, Human Genetics.

[15]  P. Schofield,et al.  The prevalence of SDHB, SDHC, and SDHD mutations in patients with head and neck paraganglioma and association of mutations with clinical features , 2004, Journal of Medical Genetics.

[16]  P. Maaswinkel-Mooy,et al.  GENOMIC IMPRINTING IN HEREDITARY GLOMUS TUMOURS: EVIDENCE FOR NEW GENETIC THEORY , 1989, The Lancet.

[17]  W. Young,et al.  Familial malignant catecholamine-secreting paraganglioma with prolonged survival associated with mutation in the succinate dehydrogenase B gene. , 2002, The Journal of clinical endocrinology and metabolism.

[18]  C. Eng,et al.  Predictors and prevalence of paraganglioma syndrome associated with mutations of the SDHC gene. , 2005, JAMA.

[19]  C. Eng,et al.  Distinct clinical features of paraganglioma syndromes associated with SDHB and SDHD gene mutations. , 2004, JAMA.