Identification of eight novel SDHB, SDHC, SDHD germline variants in Danish pheochromocytoma/paraganglioma patients

BACKGROUND: Germline mutations in the succinate dehydrogenase complex genes SDHB, SDHC, and SDHD predispose to pheochromocytomas and paragangliomas. Here, we examine the SDHB, SDHC, and SDHD mutation spectrum in the Danish population by screening of 143 Danish pheochromocytoma and paraganglioma pati...

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Autores principales: Bennedbæk, Marc, Rossing, Maria, Rasmussen, Åse K., Gerdes, Anne-Marie, Skytte, Anne-Bine, Jensen, Uffe B., Nielsen, Finn C., Hansen, Thomas v. O.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4898401/
https://www.ncbi.nlm.nih.gov/pubmed/27279923
http://dx.doi.org/10.1186/s13053-016-0053-6
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author Bennedbæk, Marc
Rossing, Maria
Rasmussen, Åse K.
Gerdes, Anne-Marie
Skytte, Anne-Bine
Jensen, Uffe B.
Nielsen, Finn C.
Hansen, Thomas v. O.
author_facet Bennedbæk, Marc
Rossing, Maria
Rasmussen, Åse K.
Gerdes, Anne-Marie
Skytte, Anne-Bine
Jensen, Uffe B.
Nielsen, Finn C.
Hansen, Thomas v. O.
author_sort Bennedbæk, Marc
collection PubMed
description BACKGROUND: Germline mutations in the succinate dehydrogenase complex genes SDHB, SDHC, and SDHD predispose to pheochromocytomas and paragangliomas. Here, we examine the SDHB, SDHC, and SDHD mutation spectrum in the Danish population by screening of 143 Danish pheochromocytoma and paraganglioma patients. METHODS: Mutational screening was performed by Sanger sequencing or next-generation sequencing. The frequencies of variants of unknown clinical significance, e.g. intronic, missense, and synonymous variants, were determined using the Exome Aggregation Consortium database, while the significance of missense mutations was predicted by in silico and loss of heterozygosity analysis when possible. RESULTS: We report 18 germline variants; nine in SDHB, six in SDHC, and three in SDHD. Of these 18 variants, eight are novel. We classify 12 variants as likely pathogenic/pathogenic, one as likely benign, and five as variants of unknown clinical significance. CONCLUSIONS: Identifying and classifying SDHB, SDHC, and SDHD variants present in the Danish population will augment the growing knowledge on variants in these genes and may support future clinical risk assessments.
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spelling pubmed-48984012016-06-09 Identification of eight novel SDHB, SDHC, SDHD germline variants in Danish pheochromocytoma/paraganglioma patients Bennedbæk, Marc Rossing, Maria Rasmussen, Åse K. Gerdes, Anne-Marie Skytte, Anne-Bine Jensen, Uffe B. Nielsen, Finn C. Hansen, Thomas v. O. Hered Cancer Clin Pract Research BACKGROUND: Germline mutations in the succinate dehydrogenase complex genes SDHB, SDHC, and SDHD predispose to pheochromocytomas and paragangliomas. Here, we examine the SDHB, SDHC, and SDHD mutation spectrum in the Danish population by screening of 143 Danish pheochromocytoma and paraganglioma patients. METHODS: Mutational screening was performed by Sanger sequencing or next-generation sequencing. The frequencies of variants of unknown clinical significance, e.g. intronic, missense, and synonymous variants, were determined using the Exome Aggregation Consortium database, while the significance of missense mutations was predicted by in silico and loss of heterozygosity analysis when possible. RESULTS: We report 18 germline variants; nine in SDHB, six in SDHC, and three in SDHD. Of these 18 variants, eight are novel. We classify 12 variants as likely pathogenic/pathogenic, one as likely benign, and five as variants of unknown clinical significance. CONCLUSIONS: Identifying and classifying SDHB, SDHC, and SDHD variants present in the Danish population will augment the growing knowledge on variants in these genes and may support future clinical risk assessments. BioMed Central 2016-06-08 /pmc/articles/PMC4898401/ /pubmed/27279923 http://dx.doi.org/10.1186/s13053-016-0053-6 Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Bennedbæk, Marc
Rossing, Maria
Rasmussen, Åse K.
Gerdes, Anne-Marie
Skytte, Anne-Bine
Jensen, Uffe B.
Nielsen, Finn C.
Hansen, Thomas v. O.
Identification of eight novel SDHB, SDHC, SDHD germline variants in Danish pheochromocytoma/paraganglioma patients
title Identification of eight novel SDHB, SDHC, SDHD germline variants in Danish pheochromocytoma/paraganglioma patients
title_full Identification of eight novel SDHB, SDHC, SDHD germline variants in Danish pheochromocytoma/paraganglioma patients
title_fullStr Identification of eight novel SDHB, SDHC, SDHD germline variants in Danish pheochromocytoma/paraganglioma patients
title_full_unstemmed Identification of eight novel SDHB, SDHC, SDHD germline variants in Danish pheochromocytoma/paraganglioma patients
title_short Identification of eight novel SDHB, SDHC, SDHD germline variants in Danish pheochromocytoma/paraganglioma patients
title_sort identification of eight novel sdhb, sdhc, sdhd germline variants in danish pheochromocytoma/paraganglioma patients
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4898401/
https://www.ncbi.nlm.nih.gov/pubmed/27279923
http://dx.doi.org/10.1186/s13053-016-0053-6
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