International initiative for a curated SDHB variant database improving the diagnosis of hereditary paraganglioma and pheochromocytoma
Year: 2021
Type: article
Abstract: Background SDHB is one of the major genes predisposing to paraganglioma/pheochromocytoma (PPGL). Identifying pathogenic SDHB variants in patients with PPGL is essential to the management of patients and relatives due to the increased risk of recurrences, metastases and the emergence of non-PPGL tumours. In this context, the ‘NGS and PPGL (NGSnPPGL) Study Group’ initiated an international effort to collect, annotate and classify SDHB variants and to provide an accurate, expert-curated and freely available SDHB variant database. Methods A total of 223 distinct SDHB variants from 737 patients were collected worldwide. Using multiple criteria, each variant was first classified according to a 5-tier grouping based on American College of Medical Genetics and NGSnPPGL standardised recommendations and was then manually reviewed by a panel of experts in the field. Results This multistep process resulted in 23 benign/likely benign, 149 pathogenic/likely pathogenic variants and 51 variants of unknown significance (VUS). Expert curation reduced by half the number of variants initially classified as VUS. Variant classifications are publicly accessible via the Leiden Open Variation Database system ( https://databases.lovd.nl/shared/genes/SDHB ). Conclusion This international initiative by a panel of experts allowed us to establish a consensus classification for 223 SDHB variants that should be used as a routine tool by geneticists in charge of PPGL laboratory diagnosis. This accurate classification of SDHB genetic variants will help to clarify the diagnosis of hereditary PPGL and to improve the clinical care of patients and relatives with PPGL.
Source: Journal of Medical Genetics
Authors: Laurene Ben Aim, Eamonn R Maher, Alberto Cascon, Anne Barlier, Sophie Giraud, Tonino Ercolino, Pascal Pigny, Roderick J Clifton-Bligh, Delphine Mirebeau-Prunier, Amira Mohamed, Judith Favier, Anne-Paule Gimenez-Roqueplo, Francesca Schiavi, Rodrigo A Toledo, Patricia L Dahia, Mercedes Robledo, Jean Pierre Bayley, Nelly Burnichon
Institutions: Assistance Publique – Hôpitaux de Paris, Hôpital Européen Georges-Pompidou, University of Cambridge, NIHR Cambridge Biomedical Research Centre, Spanish National Cancer Research Centre, Hôpital de la Conception, Hospices Civils de Lyon, Azienda Ospedaliero-Universitaria Careggi, Centre Hospitalier Universitaire de Lille, The University of Sydney, Royal North Shore Hospital, Centre Hospitalier Universitaire d'Angers, Inserm, Université Paris Cité, La Ligue Contre le Cancer, Paris Cardiovascular Research Center, Istituto Oncologico Veneto, Centro de Investigación Biomédica en Red de Cáncer, Vall d'Hebron Institute of Oncology, The University of Texas at San Antonio Health Science Center, Mays Cancer Center at UT Health San Antonio, Leiden University Medical Center
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Funders: AstraZeneca, Fundación Olga Torres, Georgia Clinical and Translational Science Alliance, Paradifference foundation, BeiGene, Hillcrest Foundation, Cancer Research UK, National Institute for Health and Care Research, University of Cambridge, Institut National de la Santé et de la Recherche Médicale, Institut National Du Cancer, Swiss Bridge Foundation, National Institutes of Health, Instituto de Salud Carlos III, National Cancer Institute, National Institute of General Medical Sciences, National Center for Advancing Translational Sciences
Awards: G1114781936, Mays Cancer Center at UT Health SA, NIHR Senior Investigator Award, G2361851875, Identificación de nuevos mecanismos de resistencia mediante secuenciación de exoma completo en ADN libre circulante: método no invasivo de mapeo de mutaciones en cáncer colorrectal refractario., Institute for Integration of Medicine & Science: A Partnership to Improve Health, G3614813735, G4087484049, G436035484, G5057425288, Mecanismos asociados a progresión de tumores endocrinos y neuroendocrinos, G7229974508, G9000068411, G9000148371, G9000150452
OpenAlex ID: W3187632149