Journal article
Tumour risks and genotype-phenotype correlations associated with germline variants in succinate dehydrogenase subunit genes SDHB, SDHC and SDHD
KA Andrews, DB Ascher, DEV Pires, DR Barnes, L Vialard, RT Casey, N Bradshaw, J Adlard, S Aylwin, P Brennan, C Brewer, T Cole, JA Cook, R Davidson, A Donaldson, A Fryer, L Greenhalgh, SV Hodgson, R Irving, F Lalloo Show all
Journal of Medical Genetics | BMJ PUBLISHING GROUP | Published : 2018
Open access
Abstract
BACKGROUND: Germline pathogenic variants in SDHB/SDHC/SDHD are the most frequent causes of inherited phaeochromocytomas/paragangliomas. Insufficient information regarding penetrance and phenotypic variability hinders optimum management of mutation carriers. We estimate penetrance for symptomatic tumours and elucidate genotype-phenotype correlations in a large cohort of SDHB/SDHC/SDHD mutation carriers. METHODS: A retrospective survey of 1832 individuals referred for genetic testing due to a personal or family history of phaeochromocytoma/paraganglioma. 876 patients (401 previously reported) had a germline mutation in SDHB/SDHC/SDHD (n=673/43/160). Tumour risks were correlated with in silico ..
View full abstractGrants
Awarded by European Commission
Funding Acknowledgements
This work was supported by the East Anglian Foundation Programme (to KAA), the University of Cambridge (KAA), NIHR Cambridge Biomedical Research Centre (KAA and ERM), Cancer Research UK Cambridge Cancer Centre (ERM), European Research Council Advanced Researcher Award (ERM), British Heart Foundation (EM), NIHR Senior Investigator Award (ERM), Newton Fund RCUK-CONFAP Grant awarded by The Medical Research Council (MRC), Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG) (to DEVP and DBA), NHMRC CJ Martin Fellowship (APP1072476) and Jack Brockhoff Foundation (JBF 4186, 2016) (to DBA), Instituto Rene Rachou (CPqRR/FIOCRUZ Minas) and Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) (to DEVP), Health Research Board Ireland (RTC) and Cancer Research - UK grant C12292/A20861 (to ACA). The University of Cambridge has received salary support in respect of EM from the NHS in the East of England through the Clinical Academic Reserve. The views expressed are those of the authors and not necessarily those of the NHS or Department of Health.