Journal article

Variant type is associated with disease characteristics in SDHB, SDHC and SDHD-linked phaeochromocytoma-paraganglioma

Jean Pierre Bayley, Birke Bausch, Johannes Adriaan Rijken, Leonie Theresia van Hulsteijn, Jeroen C Jansen, David Ascher, Douglas Eduardo Valente Pires, Frederik J Hes, Erik F Hensen, Eleonora PM Corssmit, Peter Devilee, Hartmut PH Neumann

Journal of Medical Genetics | BMJ PUBLISHING GROUP | Published : 2020


BACKGROUND: Pathogenic germline variants in subunits of succinate dehydrogenase (SDHB, SDHC and SDHD) are broadly associated with disease subtypes of phaeochromocytoma-paraganglioma (PPGL) syndrome. Our objective was to investigate the role of variant type (ie, missense vs truncating) in determining tumour phenotype. METHODS: Three independent datasets comprising 950 PPGL and head and neck paraganglioma (HNPGL) patients were analysed for associations of variant type with tumour type and age-related tumour risk. All patients were carriers of pathogenic germline variants in the SDHB, SDHC or SDHD genes. RESULTS: Truncating SDH variants were significantly over-represented in clinical cases comp..

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Awarded by Dutch Cancer Society

Awarded by Jack Brockhoff Foundation

Awarded by National Health and Medical Research Council of Australia

Funding Acknowledgements

This work was supported by the Dutch Cancer Society (Grant 2011-5025 to JPB/PD) and by the Jack Brockhoff Foundation (JBF 4186, 2016 to DA); National Health and Medical Research Council of Australia (APP1072476 to DA); Australian Cancer Research Foundation (to DA), Australia Awards - Endeavour Fellowship (to DEVP); Instituto Rene Rachou (IRR/FIOCRUZ Minas), Brazil and Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) (to DEVP); and Department of Biochemistry and Molecular Biology, University of Melbourne (to DA).