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Increased Mortality in SDHB but Not in SDHD Pathogenic Variant Carriers

Germline mutations in succinate dehydrogenase subunit B and D (SDHB and SDHD) are predisposed to hereditary paraganglioma (PGL) and pheochromocytoma (PHEO). The phenotype of pathogenic variants varies according to the causative gene. In this retrospective study, we estimate the mortality of a nation...

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Autores principales: Rijken, Johannes A., van Hulsteijn, Leonie T., Dekkers, Olaf M., Niemeijer, Nicolasine D., Leemans, C. René, Eijkelenkamp, Karin, van der Horst-Schrivers, Anouk N.A., Kerstens, Michiel N., van Berkel, Anouk, Timmers, Henri J.L.M., Kunst, Henricus P.M., Bisschop, Peter H.L.T., Dreijerink, Koen M.A., van Dooren, Marieke F., Hes, Frederik J., Jansen, Jeroen C., Corssmit, Eleonora P.M., Hensen, Erik F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356820/
https://www.ncbi.nlm.nih.gov/pubmed/30658386
http://dx.doi.org/10.3390/cancers11010103
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author Rijken, Johannes A.
van Hulsteijn, Leonie T.
Dekkers, Olaf M.
Niemeijer, Nicolasine D.
Leemans, C. René
Eijkelenkamp, Karin
van der Horst-Schrivers, Anouk N.A.
Kerstens, Michiel N.
van Berkel, Anouk
Timmers, Henri J.L.M.
Kunst, Henricus P.M.
Bisschop, Peter H.L.T.
Dreijerink, Koen M.A.
van Dooren, Marieke F.
Hes, Frederik J.
Jansen, Jeroen C.
Corssmit, Eleonora P.M.
Hensen, Erik F.
author_facet Rijken, Johannes A.
van Hulsteijn, Leonie T.
Dekkers, Olaf M.
Niemeijer, Nicolasine D.
Leemans, C. René
Eijkelenkamp, Karin
van der Horst-Schrivers, Anouk N.A.
Kerstens, Michiel N.
van Berkel, Anouk
Timmers, Henri J.L.M.
Kunst, Henricus P.M.
Bisschop, Peter H.L.T.
Dreijerink, Koen M.A.
van Dooren, Marieke F.
Hes, Frederik J.
Jansen, Jeroen C.
Corssmit, Eleonora P.M.
Hensen, Erik F.
author_sort Rijken, Johannes A.
collection PubMed
description Germline mutations in succinate dehydrogenase subunit B and D (SDHB and SDHD) are predisposed to hereditary paraganglioma (PGL) and pheochromocytoma (PHEO). The phenotype of pathogenic variants varies according to the causative gene. In this retrospective study, we estimate the mortality of a nationwide cohort of SDHB variant carriers and that of a large cohort of SDHD variant carriers and compare it to the mortality of a matched cohort of the general Dutch population. A total of 192 SDHB variant carriers and 232 SDHD variant carriers were included in this study. The Standard Mortality Ratio (SMR) for SDHB mutation carriers was 1.89, increasing to 2.88 in carriers affected by PGL. For SDHD variant carriers the SMR was 0.93 and 1.06 in affected carriers. Compared to the general population, mortality seems to be increased in SDHB variant carriers, especially in those affected by PGL. In SDHD variant carriers, the mortality is comparable to that of the general Dutch population, even if they are affected by PGL. This insight emphasizes the significance of DNA-testing in all PGL and PHEO patients, since different clinical risks may warrant gene-specific management strategies.
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spelling pubmed-63568202019-02-05 Increased Mortality in SDHB but Not in SDHD Pathogenic Variant Carriers Rijken, Johannes A. van Hulsteijn, Leonie T. Dekkers, Olaf M. Niemeijer, Nicolasine D. Leemans, C. René Eijkelenkamp, Karin van der Horst-Schrivers, Anouk N.A. Kerstens, Michiel N. van Berkel, Anouk Timmers, Henri J.L.M. Kunst, Henricus P.M. Bisschop, Peter H.L.T. Dreijerink, Koen M.A. van Dooren, Marieke F. Hes, Frederik J. Jansen, Jeroen C. Corssmit, Eleonora P.M. Hensen, Erik F. Cancers (Basel) Article Germline mutations in succinate dehydrogenase subunit B and D (SDHB and SDHD) are predisposed to hereditary paraganglioma (PGL) and pheochromocytoma (PHEO). The phenotype of pathogenic variants varies according to the causative gene. In this retrospective study, we estimate the mortality of a nationwide cohort of SDHB variant carriers and that of a large cohort of SDHD variant carriers and compare it to the mortality of a matched cohort of the general Dutch population. A total of 192 SDHB variant carriers and 232 SDHD variant carriers were included in this study. The Standard Mortality Ratio (SMR) for SDHB mutation carriers was 1.89, increasing to 2.88 in carriers affected by PGL. For SDHD variant carriers the SMR was 0.93 and 1.06 in affected carriers. Compared to the general population, mortality seems to be increased in SDHB variant carriers, especially in those affected by PGL. In SDHD variant carriers, the mortality is comparable to that of the general Dutch population, even if they are affected by PGL. This insight emphasizes the significance of DNA-testing in all PGL and PHEO patients, since different clinical risks may warrant gene-specific management strategies. MDPI 2019-01-17 /pmc/articles/PMC6356820/ /pubmed/30658386 http://dx.doi.org/10.3390/cancers11010103 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Rijken, Johannes A.
van Hulsteijn, Leonie T.
Dekkers, Olaf M.
Niemeijer, Nicolasine D.
Leemans, C. René
Eijkelenkamp, Karin
van der Horst-Schrivers, Anouk N.A.
Kerstens, Michiel N.
van Berkel, Anouk
Timmers, Henri J.L.M.
Kunst, Henricus P.M.
Bisschop, Peter H.L.T.
Dreijerink, Koen M.A.
van Dooren, Marieke F.
Hes, Frederik J.
Jansen, Jeroen C.
Corssmit, Eleonora P.M.
Hensen, Erik F.
Increased Mortality in SDHB but Not in SDHD Pathogenic Variant Carriers
title Increased Mortality in SDHB but Not in SDHD Pathogenic Variant Carriers
title_full Increased Mortality in SDHB but Not in SDHD Pathogenic Variant Carriers
title_fullStr Increased Mortality in SDHB but Not in SDHD Pathogenic Variant Carriers
title_full_unstemmed Increased Mortality in SDHB but Not in SDHD Pathogenic Variant Carriers
title_short Increased Mortality in SDHB but Not in SDHD Pathogenic Variant Carriers
title_sort increased mortality in sdhb but not in sdhd pathogenic variant carriers
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356820/
https://www.ncbi.nlm.nih.gov/pubmed/30658386
http://dx.doi.org/10.3390/cancers11010103
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