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Renal Cancer
Published in Karl H. Pang, Nadir I. Osman, James W.F. Catto, Christopher R. Chapple, Basic Urological Sciences, 2021
Sabrina H. Rossi, Grant D. Stewart
Gene function:Succinate dehydrogenase (SDH): tetrameric enzyme in the Krebs cycle, upstream to fumarate hydratase.Each four SDH subunits are encoded by four genes:SDHA, SDHB, SDHC, and SDHDMutations in the SDHB gene are the most common.
Hereditary Pheochromocytoma and Paraganglioma Syndrome
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
The SDHD (succinate dehydrogenase complex subunit D) gene encodes one of two integral membrane proteins anchoring the complex to the matrix side of the mitochondrial inner membrane. Mutations in SDHD lead to hereditary paraganglioma, which is transmitted almost exclusively through the paternal allele. It is notable that three SDHD pathogenic variants (p.Asp92Tyr, p.Leu95Pro, p.Leu139Pro) are implicated in nearly all hereditary paraganglioma cases in the Dutch population, whereas SDHD pathogenic variant p.Met1Ile is a founder variant in the Chinese population [2].
Cardiac and cardiovascular disorders
Published in Angus Clarke, Alex Murray, Julian Sampson, Harper's Practical Genetic Counselling, 2019
Familial glomus tumours (paragangliomas) provide an unusual example of autosomal dominant inheritance modified by genetic imprinting (see Chapter 32). One of the two genes often involved (SDHD) results in the disorder being expressed only when transmitted paternally.
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
Series from the Netherlands has shown that SDHD mutations are highly penetrant and paternally inherited (i.e. maternal imprinting). [7] HNPGLs are a common manifestation of SDHD-associated disease, and SDHD-affected carriers are also at risk of pheochromocytomas, other abdominal and thoracic paragangliomas, as well as renal cell carcinoma, gastrointestinal stromal tumours, and pituitary adenomas. Traditionally, SDHD has been reported to account for the majority of SDH-associated paragangliomas, both sporadic and familial cases, in previously published European and American series. However, a recent series of 101 patients from a highly consanguineous cohort from Saudi Arabia reported that the SDHB gene was the most common cause of genetic extra-abdominal paragangliomas. [10] Another recent series from Japan showed that 81 of 327 (32%) patients with abdominal and extra-abdominal paragangliomas had pathogenic or likely pathogenic variants, and the most frequently mutated gene was SDHB (57, 15.4%), followed by SDHD (27, 7.3%), and the incidence of metastatic disease was high in SDHB carriers (21/57, 36.8%). [9] The four subjects in our series with SDH-associated GJ were of mixed race of Hispanic descent, and the most common mutated gene was SDHC. This and other reports in non-Caucasian populations highlight significant ethnic differences in terms of the prevalence of susceptibility genes responsible for HNPGL.
Head and neck paragangliomas in Norway, importance of genetics, updated diagnostic workup and treatment
Published in Acta Oto-Laryngologica, 2021
Mohammad Usman Rana, Arild André Østhus, Ketil Heimdal, Peter Jebsen, Mona-Elisabeth R. Revheim, Terje Andreas Osnes
Authoritative reports conclude that genetic testing for mutations must be an integral part of the work-up for all PG patients, for several reasons [12]. PGs that appear sporadic, with a negative family history, might in reality be hereditary. This may be due to a combination of factors including the occurrence of new mutations, reduced penetrance, imprinting in SDHD-related PG, and lack of appreciation among patients and doctors that certain combinations of tumours in different family members may signal heritability. Discovering a hereditary form of head and neck PG is deemed valuable, because it may help to estimate the risk of recurrence, malignancy, multifocality, pattern of inheritance/risk to relatives including risk of relevant syndromes. SDHB mutations have been reported to carry a higher risk of malignancy [13]; nevertheless, this is not reflected in our study. SDHD mutations are associated with multifocal PGs, and according to Boedeker et al., multifocal PGs are present in the vast majority of the SDHD patients [3]. In our study, we found that 88% of the patients with SDHD mutations had multifocal PG disease. Other benefits of discovering PG related mutations are the possibility of providing genetic counselling for particularly 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
The reported rate of SDH mutations in PGLs varies significantly between series, ranging from 15% to 54%.15,25 Mutations in SDHB and SDHD are the most common of the four subunits and correspond to syndromes PGL4 and PGL1 respectively.26 SDHB mutated tumours (PGL4) are usually abdominal and have the highest risk of metastases. Up to 71% of paragangliomas with SDHB mutations have been shown to metastasise compared with only 3% of non-SDHB mutated cases.14,15 Furthermore, SDHB mutations, which show incomplete penetrance, result in tumours at younger ages.27 In contrast, tumours with SDHD mutations are typically found in the head and neck region, and are multiple and recurrent with a very low rate of metastases.28