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Endocrine and Neuroendocrine Tumors
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
Natasha Shrikrishnapalasuriyar, P.N. Plowman, Márta Korbonits, Ashley B. Grossman
The other genes shown in Table 5.3 include TMEM127 and MAX, while in many cases the germline syndromes predispose to paragangliomas rather than pheochromocytomas. Paragangliomas are more often prone to metastasis than pheochromocytomas, and are less often secretory. Approaching 20 germlines genes have been identified to date with these tumors.
Hereditary Pheochromocytoma and Paraganglioma Syndrome
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
Overall, germline pathogenic variants in SDHB, SDHD, VHL, RET, or NF1 account for 90% of hereditary PPGL cases, and SDHC, SDHA, SDGAF2, TMEM127, or MAX (1.2%) mutations are responsible for only 10% of such cases [2].
Endocrine hypertension
Published in Philip E. Harris, Pierre-Marc G. Bouloux, Endocrinology in Clinical Practice, 2014
Frances McManus, John M. Connell, Marie Freel
The genetics of pheochromocytoma and paraganglioma is a rapidly changing and evolving field. For example, in 2010, loss-of-function mutations in the FP/TMEM127 gene were identified in 2% of patients with familial and sporadic pheochromocytoma, but not paraganglioma. TMEM127 is a negative regulator of mammalian target of rapamycin (mTOR) effector proteins.65 In addition, mutations within the SDH5 (SDHA2) gene have recently been identified as causing familial paraganglioma syndromes in one kindred first identified in the 1980s.66 SDH5 is important for the flavination and function of SDHA. However, this genetic syndrome remains extremely rare, and only one further kindred has been identified so far.
Genotype-phenotype associations in paragangliomas of the temporal bone in a multi-ethnic cohort
Published in Acta Oto-Laryngologica, 2023
Simon I. Angeli, Juan A. Chiossone K, Stefania Goncalves, Fred F. Telischi
Mutation analyses were conducted as part of the patient’s clinical care in a CLIA-certified laboratory (Invitae, San Francisco, California, USA). After obtaining informed consent from the patients, genomic DNA was isolated from blood leukocytes or cheek swabs and enriched for targeted regions using a hybridization-based protocol and sequenced using Illumina technology. The targeted regions that were sequenced and evaluated for sequence changes and exonic deletion/duplications involved the following genes: SDHB (8 exons), SDHC (6 exons), SDHD (4 exons), SDHAF2, RET, NF1, VHL, TMEM127, and MAX. The SDHA gene was evaluated for sequence changes only. The reference sequence was GRCh37. When a TBPGL patient is found to have a pathologic germline mutation, clinical and genetic screening was offered to first degree relatives.
Prevalence of succinate dehydrogenase deficiency in paragangliomas and phaeochromocytomas at a tertiary hospital in Cape Town: a retrospective review
Published in Journal of Endocrinology, Metabolism and Diabetes of South Africa, 2021
Cassandra Bruce-Brand, Abraham C van Wyk
PGLs and PCs can occur sporadically or as hereditary tumours with up to 40% occurring as a result of germline mutations in susceptibility genes.2,3 Research conducted in the nineteenth and twentieth centuries led to the recognition of three PC/PGL-associated syndromes: von Hippel-Lindau (VHL) disease, multiple endocrine neoplasia type 2 (RET) and neurofibromatosis type 1 (NF1).4–9 Between 2000 and 2010, the molecular basis for hereditary PC/PGL syndrome was discovered to be due to mutations in succinate dehydrogenase (SDH) subunits and related genes.10–16 New susceptibility genes causing hereditary PC/PGL syndrome discovered over the past ten years included MAX, TMEM127, EGLN, HIF2α, MET and KIF1B.2 Currently these susceptibility genes are grouped into two categories: major susceptibility genes including NF1, VHL, RET and SHDB/D and minor susceptibility genes including SDHA/C, SDHAF2, MAX and TMEM127.3,17 The major susceptibility genes account for up to 90% of the hereditary tumours, the minor group accounts for the other 10%.3,17
Cost-minimization analysis of sequential genetic testing versus targeted next-generation sequencing gene panels in patients with pheochromocytoma and paraganglioma
Published in Annals of Medicine, 2021
Weenita Pipitprapat, Oraluck Pattanaprateep, Nareenart Iemwimangsa, Insee Sensorn, Bhakbhoom Panthan, Poramate Jiaranai, Wasun Chantratita, Kinnaree Sorapipatcharoen, Preamrudee Poomthavorn, Pat Mahachoklertwattana, Thanyachai Sura, Atchara Tunteeratum, Kanoknan Srichan, Chutintorn Sriphrapradang
We developed a custom-designed multigene panel, which covers 17 susceptibility genes related to syndromic PPGL or hereditary PPGL (BAP1, EGLN1, EPAS1, FH, KIF1B, KMT2D, MAX, MEN1, NF1, RET, SDHA, SDHAF2, SDHB, SDHC, SDHD, TMEM127, VHL) including exon–intron boundaries. Variant annotation was performed with VarSeq® Software version 2.1.1 (Golden Helix Inc., Bozeman, MT). Variants were filtered based on in-house developed PPGL gene list and minor allele frequency (MAF) of less than 0.05 across the online database (e.g. gnomAD, 1000 Genomes, ExAC, dbSNP, and ClinVar) and in-house Thai database (455 persons). Using the American College of Medical Genetics and Genomics (ACMG) 2015 variant classification guidelines together with Varsome® Software (Saphetor, Lausanne, Switzerland), the clinical interpretation of selected variants was determined. Computational and prediction data using in silico tools were done as one of the ACMG criteria. Variants that were classified as pathogenic or likely pathogenic were considered to be definite causes of PPGL in the patients. Variants that did not meet the criteria of pathogenic, likely pathogenic, benign, or likely benign, would be classified as variant of uncertain significance (VUS). Variants found using NGS were subsequently validated by Sanger sequencing. The genotype–phenotype correlation of PPGL was analyzed.