Assessment of gene–disease associations and recommendations for genetic testing for somatic variants in vascular anomalies by VASCERN-VASCA
(2024) Orphanet Journal of Rare Diseases — Vol. 19, n° 1, p. 213 [1-14] (2024)
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- Authors
Bracquemart, Claire 
Alhopuro, Pia Michiels, Rodolphe
- Abstract
- (en) 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: 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: 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/ ).
- Affiliations
Radboud University Medical Center Department of Pathology CHU Caen Normandie Service de Génétique University of Helsinki Laboratory of Genetics Institut de Recerca Sant Joan de Déu Genomic Unit Hospital Sant Joan de Deu Department of Dermatology Bambino Gesù Children Hospital and Research Institute Laboratory of Medical Geneticsogy Sorbonne Université Département de Génétique Karolinska Institutet and Department of Clinical Genetics Department of Molecular Medicine and Surgery Copenhagen University Hospital - Rigshospitalet Department of Genetics, Center of Diagnostics Hospital Sant Joan de Déu Laboratory of Molecular Oncology University of Helsinki Department of Clinical Genetics Oslo University Hospital Department of Medical Genetics Bambino Gesù Children Hospital and Research Institute Laboratory of Medical Genetics University Hospital Otto-Von-Guericke-University Institute of Human Genetics WEL Research Institute WELBIO Department
Citations
Revencu, N., Eijkelenboom, A., Bracquemart, C., Alhopuro, P., Armstrong, J., Baselga, E., Cesario, C., Dentici, M. L., Eyries, M., Frisk, S., Karstensen, H. G., Gene-Olaciregui, N., Kivirikko, S., Lavarino, C., Mero, I.-L., Michiels, R., Pisaneschi, E., Schönewolf-Greulich, B., Wieland, I., et al. (2024). Assessment of gene–disease associations and recommendations for genetic testing for somatic variants in vascular anomalies by VASCERN-VASCA. Orphanet Journal of Rare Diseases, 19(1), 213 [1-14]. https://doi.org/10.1186/s13023-024-03196-9 (Original work published 2024)