Assessment of gene-disease associations and recommendations for genetic testing for somatic variants in vascular anomalies by VASCERN-VASCA.

Humans Genetic Testing / methods Vascular Malformations / genetics Genetic Association Studies
ERN Gene curation ISSVA Mosaic Postzygotic Precision medicine Somatic VASCERN-VASCA Vascular malformation

Journal

Orphanet journal of rare diseases
ISSN: 1750-1172
Titre abrégé: Orphanet J Rare Dis
Pays: England
ID NLM: 101266602

Informations de publication

Date de publication:
22 May 2024
Historique:
received: 12 12 2023
accepted: 19 04 2024
medline: 23 5 2024
pubmed: 23 5 2024
entrez: 22 5 2024
Statut: epublish

Résumé

Vascular anomalies caused by somatic (postzygotic) variants are clinically and genetically heterogeneous diseases with overlapping or distinct entities. The genetic knowledge in this field is rapidly growing, and genetic testing is now part of the diagnostic workup alongside the clinical, radiological and histopathological data. Nonetheless, access to genetic testing is still limited, and there is significant heterogeneity across the approaches used by the diagnostic laboratories, with direct consequences on test sensitivity and accuracy. The clinical utility of genetic testing is expected to increase progressively with improved theragnostics, which will be based on information about the efficacy and safety of the emerging drugs and future molecules. The aim of this study was to make recommendations for optimising and guiding the diagnostic genetic testing for somatic variants in patients with vascular malformations. Physicians and lab specialists from 11 multidisciplinary European centres for vascular anomalies reviewed the genes identified to date as being involved in non-hereditary vascular malformations, evaluated gene-disease associations, and made recommendations about the technical aspects for identification of low-level mosaicism and variant interpretation. A core list of 24 genes were selected based on the current practices in the participating laboratories, the ISSVA classification and the literature. In total 45 gene-phenotype associations were evaluated: 16 were considered definitive, 16 strong, 3 moderate, 7 limited and 3 with no evidence. This work provides a detailed evidence-based view of the gene-disease associations in the field of vascular malformations caused by somatic variants. Knowing both the gene-phenotype relationships and the strength of the associations greatly help laboratories in data interpretation and eventually in the clinical diagnosis. This study reflects the state of knowledge as of mid-2023 and will be regularly updated on the VASCERN-VASCA website (VASCERN-VASCA, https://vascern.eu/groupe/vascular-anomalies/ ).

Sections du résumé

BACKGROUND BACKGROUND
Vascular anomalies caused by somatic (postzygotic) variants are clinically and genetically heterogeneous diseases with overlapping or distinct entities. The genetic knowledge in this field is rapidly growing, and genetic testing is now part of the diagnostic workup alongside the clinical, radiological and histopathological data. Nonetheless, access to genetic testing is still limited, and there is significant heterogeneity across the approaches used by the diagnostic laboratories, with direct consequences on test sensitivity and accuracy. The clinical utility of genetic testing is expected to increase progressively with improved theragnostics, which will be based on information about the efficacy and safety of the emerging drugs and future molecules. The aim of this study was to make recommendations for optimising and guiding the diagnostic genetic testing for somatic variants in patients with vascular malformations.
RESULTS RESULTS
Physicians and lab specialists from 11 multidisciplinary European centres for vascular anomalies reviewed the genes identified to date as being involved in non-hereditary vascular malformations, evaluated gene-disease associations, and made recommendations about the technical aspects for identification of low-level mosaicism and variant interpretation. A core list of 24 genes were selected based on the current practices in the participating laboratories, the ISSVA classification and the literature. In total 45 gene-phenotype associations were evaluated: 16 were considered definitive, 16 strong, 3 moderate, 7 limited and 3 with no evidence.
CONCLUSIONS CONCLUSIONS
This work provides a detailed evidence-based view of the gene-disease associations in the field of vascular malformations caused by somatic variants. Knowing both the gene-phenotype relationships and the strength of the associations greatly help laboratories in data interpretation and eventually in the clinical diagnosis. This study reflects the state of knowledge as of mid-2023 and will be regularly updated on the VASCERN-VASCA website (VASCERN-VASCA, https://vascern.eu/groupe/vascular-anomalies/ ).

Identifiants

DOI: 10.1186/s13023-024-03196-9 PMID: 38778413
pubmed: 38778413
doi: 10.1186/s13023-024-03196-9
pii: 10.1186/s13023-024-03196-9
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

213

Subventions

Organisme : Bundesministerium für Bildung und Forschung
ID : FKZ 01GM1902A
Organisme : Bundesministerium für Bildung und Forschung
ID : FKZ 01GM1921A
Organisme : Fonds De La Recherche Scientifique - FNRS
ID : T.0240.23
Organisme : Fonds De La Recherche Scientifique - FNRS
ID : P.C005.22
Organisme : Koning Boudewijnstichting
ID : 2018-J1810250-211305
Organisme : Gouvernement Wallon
ID : WELBIO-CR-2019C-06

Informations de copyright

© 2024. The Author(s).

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Auteurs

Nicole Revencu (N)

Center for Human Genetics, Cliniques universitaires Saint-Luc, University of Louvain, VASCERN VASCA European Reference Centre, Brussels, Belgium.
ORCID: 0000-0002-7120-4903

Astrid Eijkelenboom (A)

Department of Pathology, Radboud University Medical Center, VASCERN VASCA European Reference Centre, PO Box 9101, 6500, HB, Nijmegen, the Netherlands.

Claire Bracquemart (C)

Normandie Univ, UNICAEN, Service de Génétique, CHU Caen Normandie, BIOTARGEN EA 7450, VASCERN VASCA European Reference Centre, Caen, 14000, France.
ORCID: 0000-0003-2096-6702

Pia Alhopuro (P)

HUS Diagnostic Center, Laboratory of Genetics, University of Helsinki and Helsinki University Hospital, VASCERN VASCA European Reference Centre, Helsinki, Finland.
ORCID: 0000-0001-5745-0449

Judith Armstrong (J)

Institut de Recerca Sant Joan de Déu, Esplugues de Llobregat, CIBER-ER (Biomedical Network Research Center for Rare Diseases), Instituto de Salud Carlos III (ISCIII), Madrid, and Genomic Unit, Molecular and Genetic Medicine Section, Hospital Sant Joan de Déu, VASCERN VASCA European Reference Centre, Barcelona, Spain.

Eulalia Baselga (E)

Department of Dermatology, Hospital Sant Joan de Deu, VASCERN VASCA European Reference Centre, Barcelona, Spain.
ORCID: 0000-0003-1086-8439

Claudia Cesario (C)

Laboratory of Medical Genetics, Translational Cytogenomics Research Unit, Bambino Gesù Children Hospital and Research Institute, IRCCS, VASCERN VASCA European Reference Centre, Rome, Italy.
ORCID: 0000-0002-6305-3316

Maria Lisa Dentici (ML)

Medical Genetics Unit, Bambino Gesù Children's Hospital, IRCCS, VASCERN VASCA European Reference Centre, 00165, Rome, Italy.

Melanie Eyries (M)

Sorbonne Université, Département de Génétique, Assistance Publique-Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, VASCERN VASCA European Reference Centre, Paris, France.
ORCID: 0000-0003-1911-6698

Sofia Frisk (S)

Department of Molecular Medicine and Surgery, Karolinska Institutet and Department of Clinical Genetics, Karolinska University Hospital, VASCERN VASCA European Reference Centre, Stockholm, Sweden.
ORCID: 0000-0002-2416-462X

Helena Gásdal Karstensen (HG)

Department of Genetics, Center of Diagnostics, Copenhagen University Hospital - Rigshospitalet, VASCERN VASCA European Reference Centre, Copenhagen, Denmark.
ORCID: 0000-0002-3871-969X

Nagore Gene-Olaciregui (N)

Laboratory of Molecular Oncology, Pediatric Cancer Center Barcelona, Hospital Sant Joan de Déu, VASCERN VASCA European Reference Centre, Barcelona, Spain.

Sirpa Kivirikko (S)

Department of Clinical Genetics, HUS Diagnostic Center, University of Helsinki and Helsinki University Hospital, VASCERN VASCA European Reference Centre, Helsinki, Finland.
ORCID: 0000-0002-9926-8802

Cinzia Lavarino (C)

Laboratory of Molecular Oncology, Pediatric Cancer Center Barcelona, Hospital Sant Joan de Déu, VASCERN VASCA European Reference Centre, Barcelona, Spain.
ORCID: 0000-0002-9630-3676

Inger-Lise Mero (IL)

Department of Medical Genetics, Oslo University Hospital, VASCERN VASCA European Reference Centre, Oslo, Norway.

Rodolphe Michiels (R)

Center for Human Genetics, Cliniques universitaires Saint-Luc, University of Louvain, VASCERN VASCA European Reference Centre, Brussels, Belgium.
ORCID: 0000-0003-3919-7317

Elisa Pisaneschi (E)

Laboratory of Medical Genetics, Translational Cytogenomics Research Unit, Bambino Gesù Children Hospital and Research Institute, IRCCS, VASCERN VASCA European Reference Centre, Rome, Italy.
ORCID: 0000-0001-5912-8269

Bitten Schönewolf-Greulich (B)

Department of Genetics, Center of Diagnostics, Copenhagen University Hospital - Rigshospitalet, VASCERN VASCA European Reference Centre, Copenhagen, Denmark.
ORCID: 0000-0003-0088-0792

Ilse Wieland (I)

Institute of Human Genetics, University Hospital Otto-Von-Guericke-University, Magdeburg, Germany.

Martin Zenker (M)

Institute of Human Genetics, University Hospital Otto-Von-Guericke-University, Magdeburg, Germany.
ORCID: 0000-0003-1618-9269

Miikka Vikkula (M)

Center for Vascular Anomalies, Cliniques Universitaires Saint-Luc, Brussels, Belgium. miikka.vikkula@uclouvain.be.
Human Molecular Genetics , de Duve Institute, University of Louvain, VASCERN VASCA European Reference Centre, Brussels, Belgium. miikka.vikkula@uclouvain.be.
WELBIO Department, WEL Research Institute, Avenue Pasteur, 6, 1300, Wavre, Belgium. miikka.vikkula@uclouvain.be.
ORCID: 0000-0002-6236-338X

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