Hanson, Helen, Durkie, Miranda, Lalloo, Fiona, Izatt, Louise, McVeigh, Terri P., Cook, Jackie A., Brewer, Carole, Drummond, James, Cranston, Treena, Butler, Samantha, Casey, Ruth, Tan, Tricia, Morganstein, Daniel, Eccles, Diana M., Tischkowitz, Marc, Turnbull, Clare, Woodward, Emma Roisin and Maher, Eamonn R. (2023). UK recommendations for SDHA germline genetic testing and surveillance in clinical practice. Journal of Medical Genetics, 60 (2), pp. 107-111.
Abstract
SDHA pathogenic germline variants (PGVs) are identified in up to 10% of patients with paraganglioma and phaeochromocytoma and up to 30% with wild-type gastrointestinal stromal tumours. Most SDHA PGV carriers present with an apparently sporadic tumour, but often the pathogenic variant has been inherited from parent who has the variant, but has not developed any clinical features. Studies of SDHA PGV carriers suggest that lifetime penetrance for SDHA-associated tumours is low, particularly when identified outside the context of a family history. Current recommended surveillance for SDHA PGV carriers follows an intensive protocol. With increasing implementation of tumour and germline large panel and whole-genome sequencing, it is likely more SDHA PGV carriers will be identified in patients with tumours not strongly associated with SDHA, or outside the context of a strong family history. This creates a complex situation about what to recommend in clinical practice considering low penetrance for tumour development, surveillance burden and patient anxiety. An expert SDHA working group was formed to discuss and consider this situation. This paper outlines the recommendations from this working group for testing and management of SDHA PGV carriers in clinical practice.
Publication DOI: | https://doi.org/10.1136/jmedgenet-2021-108355 |
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Divisions: | College of Health & Life Sciences > Aston Medical School |
Funding Information: | HH and FL are supported by Cancer Research CRUK Catalyst Award, CanGene-CanVar (C61296/A27223). RC is supported by GIST Support UK. ERW is supported by the Manchester NIHR Biomedical Research Centre (IS-BRC-1215-20007). ERM thanks the NIHR Cambridge Biome |
Additional Information: | Copyright © Author(s) (or their employer(s)), 2023. Re-use permitted under CC BY. Published by BMJ. |
Uncontrolled Keywords: | Humans,Genetic Testing,Paraganglioma/genetics,Pheochromocytoma/genetics,Germ-Line Mutation/genetics,Adrenal Gland Neoplasms/genetics,United Kingdom,Genetic Predisposition to Disease,Electron Transport Complex II/genetics |
Publication ISSN: | 1468-6244 |
Last Modified: | 06 Aug 2024 09:58 |
Date Deposited: | 04 Jan 2024 10:24 |
Full Text Link: | |
Related URLs: |
http://www.scop ... tnerID=8YFLogxK
(Scopus URL) https://jmg.bmj ... ontent/60/2/107 (Publisher URL) |
PURE Output Type: | Article |
Published Date: | 2023-01-24 |
Published Online Date: | 2022-03-08 |
Accepted Date: | 2022-02-13 |
Authors: |
Hanson, Helen
Durkie, Miranda Lalloo, Fiona Izatt, Louise McVeigh, Terri P. Cook, Jackie A. Brewer, Carole Drummond, James Cranston, Treena Butler, Samantha Casey, Ruth Tan, Tricia Morganstein, Daniel Eccles, Diana M. Tischkowitz, Marc Turnbull, Clare Woodward, Emma Roisin Maher, Eamonn R. |