title: Novel SDHB and TMEM127 Mutations in Patients with Pheochromocytoma/Paraganglioma Syndrome.
abstract: Pheochromocytomas (Pheo) and paragangliomas (PGL) are rare tumors, with heterogeneous genetic background. In up to 30 % of all, apparently sporadic Pheo/PGL cases germline mutations can be identified in one of the 15 genes representing genetic susceptibility for Pheo/PGL. Malignancy is rare but it frequently associates with SDHB mutations. Our aim was to determine the prevalence of germline SDHx, SDHAF2, MAX and TMEM127 mutations in Hungarian patients with apparently sporadic Pheo/PGLs. Mutation screening of the SDHx, SDHAF2, MAX and TMEM127 genes was performed in 82 Hungarian patients with apparently sporadic Pheo/PGL using PCR and bidirectional Sanger sequencing. Disease-causing germline mutations were identified in 11 patients, of which 4 SDHB and 2 TMEM127 mutations were novel. Earlier development of Pheo/PGL, more malignant phenotype and multiple tumors were observed in genetically positive cases especially in those with SDHB mutations. The presence of bilateral or multiple tumors was the most predictive for identification of a pathogenic mutation. Together with cases harboring germline RET, VHL and NF1 mutations, Hungarian patients with Pheo/PGL exhibit a heterogeneous mutation spectrum, indicating that all of the Pheo/PGL susceptibility genes should be tested. Novel genotype-phenotype associations revealed by our study may contribute to improvement of diagnostic approaches and may help to achieve a better clinical follow up for patients with Pheo/PGL.
authors.affiliation: HAS-SE "Lendulet" Hereditary Endocrine Tumors Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary. patocs.attila@med.semmelweis-univ.hu.|Bionics Innovation Center, Budapest, Hungary. patocs.attila@med.semmelweis-univ.hu.|Department of Laboratory Medicine, Semmelweis University, Budapest, Hungary. patocs.attila@med.semmelweis-univ.hu.
authors.forename: Attila
authors.initials: A
authors.lastname: Patócs
authors.affiliation: HAS-SE "Lendulet" Hereditary Endocrine Tumors Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary.|2nd Department of Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Nikoletta K
authors.initials: NK
authors.lastname: Lendvai
authors.affiliation: HAS-SE "Lendulet" Hereditary Endocrine Tumors Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary.|HAS-SE Molecular Medicine Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary.
authors.forename: Henriett
authors.initials: H
authors.lastname: Butz
authors.affiliation: HAS-SE "Lendulet" Hereditary Endocrine Tumors Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary.
authors.forename: Istvan
authors.initials: I
authors.lastname: Liko
authors.affiliation: Department of 1st Pathology and Experimental Oncology, Semmelweis University, Budapest, Hungary.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Sapi
authors.affiliation: 2nd Department of Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Nikolette
authors.initials: N
authors.lastname: Szucs
authors.affiliation: Ferenc Markhot County Hospital, Eger, Hungary.
authors.forename: Geza
authors.initials: G
authors.lastname: Toth
authors.affiliation: HAS-SE "Lendulet" Hereditary Endocrine Tumors Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary.|2nd Department of Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Vince K
authors.initials: VK
authors.lastname: Grolmusz
authors.affiliation: 2nd Department of Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Peter
authors.initials: P
authors.lastname: Igaz
authors.affiliation: 2nd Department of Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Miklos
authors.initials: M
authors.lastname: Toth
authors.affiliation: Bionics Innovation Center, Budapest, Hungary.|2nd Department of Medicine, Semmelweis University, Budapest, Hungary.|HAS-SE Molecular Medicine Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary.
authors.forename: Károly
authors.initials: K
authors.lastname: Rácz
mesh_terms: D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000235:genetics*; D000328:Adult; D000368:Aged; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing / Q000379:methods; D005838:Genotype; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D006814:Hungary; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D010235:Paraganglioma / Q000235:genetics*; D010641:Phenotype; D010673:Pheochromocytoma / Q000235:genetics*; D013385:Succinate Dehydrogenase / Q000235:genetics*; D055815:Young Adult
chemical_list: D008565:Membrane Proteins; C548370:TMEM127 protein, human; C108095:SDHB protein, human; D013385:Succinate Dehydrogenase
keywords: Genotype-phenotype; Germline mutation; Paraganglioma; Pheochromocytoma