Non-Hotspot PIK3CA Variants Have Higher Variant Allele Frequency and are More Common in Syndromic Vascular Malformations.

PIK3CA PI3K pathogenic variant somatic mutation vascular malformation

Journal

American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741

Informations de publication

Date de publication:
07 Oct 2024
Historique:
revised: 29 07 2024
received: 27 04 2024
accepted: 06 09 2024
medline: 8 10 2024
pubmed: 8 10 2024
entrez: 8 10 2024
Statut: aheadofprint

Résumé

PIK3CA variants are known to cause vascular malformations. We were interested in studying the phenotypic spectrum, the location within the PIK3CA gene, and the variant allele frequency (VAF) of somatic PI3KCA variants in vascular malformations. Clinical data of consecutive patients with extracranial/extraspinal vascular malformations were collected in the context of the VASCOM cohort (2008-2022, n = 558). Starting October 2020, biopsy samples were tested with the TSO500 gene panel (Illumina). All consenting patients with PIK3CA variants were included in this study. Eighty-nine patients had available genetic results by June 2022. PIK3CA variants (n = 25) were found in 16 simple/combined (nonsyndromic) vascular malformations and in nine vascular malformations associated with other anomalies (syndromic). Four hotspot variants in exons 9 and 20 (c.1624G>A, c.1633G>A, c.3140A>G, c.3140A>T) were identified in 16/25 patients (VAF 0.9%-9.7%). Six non-hotspot variants (c.328_330del, c.323_337del, c.353G>A, c.1258T>C, c.3132T>A, c.3195_3203delinsT) were detected in nine patients (VAF 3.6%-31.7%). Non-hotspot variants were more frequent in syndromic than nonsyndromic vascular malformations (p = 0.0034) and exhibited a higher VAF than hotspot variants (p = 0.0253). Our study contributes to the growing body of knowledge of the genetic background in vascular malformations. Further studies will enrich the ever-growing list of pathogenic PIK3CA variants associated with vascular malformations.

Identifiants

DOI: 10.1002/ajmg.a.63883 PMID: 39376044
pubmed: 39376044
doi: 10.1002/ajmg.a.63883
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e63883

Subventions

Organisme : Swiss National Science Foundation
ID : CRSII5_193694 2021-2024
Pays : Switzerland

Informations de copyright

© 2024 The Author(s). American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.

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Auteurs

Themis-Areti A Andreoti (TA)

Division of Pediatric Hematology and Oncology, Department of Pediatrics, Inselspital - University Hospital of Bern, University of Bern, Bern, Switzerland.
Graduate School for Health Sciences, University of Bern, Bern, Switzerland.

Massimo Maiolo (M)

Division of Angiology, Swiss Cardiovascular Center, Inselspital - University Hospital of Bern, University of Bern, Bern, Switzerland.
Institute of Tissue Medicine and Pathology, University of Bern, Bern, Switzerland.
SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland.

Aleksandra Tuleja (A)

Graduate School for Health Sciences, University of Bern, Bern, Switzerland.
Division of Angiology, Swiss Cardiovascular Center, Inselspital - University Hospital of Bern, University of Bern, Bern, Switzerland.

Yvonne Döring (Y)

Division of Angiology, Swiss Cardiovascular Center, Inselspital - University Hospital of Bern, University of Bern, Bern, Switzerland.
Department for BioMedical Research (DBMR), University of Bern, Bern, Switzerland.
Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University Munich (LMU), Munich, Germany.
DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany.

André Schaller (A)

Department of Human Genetics, Inselspital - University Hospital of Bern, University of Bern, Bern, Switzerland.

Erik Vassella (E)

Institute of Tissue Medicine and Pathology, University of Bern, Bern, Switzerland.

Laurence M Boon (LM)

Center for Vascular Anomalies, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
VASCERN (European Network of Rare Vascular Diseases) Reference Center, VASCA Working Group, Brussels, Belgium.

Iris Baumgartner (I)

Vasc Alliance AG, Bern, Switzerland.
Bern Center for Vascular Medicine and Interventions, Bern, Switzerland.

Sarah M Bernhard (SM)

Division of Angiology, Swiss Cardiovascular Center, Inselspital - University Hospital of Bern, University of Bern, Bern, Switzerland.
Department for BioMedical Research (DBMR), University of Bern, Bern, Switzerland.
Vascular Center, Bienna Hospital Center, Bienna, Switzerland.

Christiane Zweier (C)

Department of Human Genetics, Inselspital - University Hospital of Bern, University of Bern, Bern, Switzerland.
ORCID: 0000-0001-8002-2020

Miikka Vikkula (M)

Center for Vascular Anomalies, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
VASCERN (European Network of Rare Vascular Diseases) Reference Center, VASCA Working Group, Brussels, Belgium.
Department of Human Genetics, Laboratory of Human Molecular Genetics, de Duve Institute, Catholic University of Louvain, Brussels, Belgium.
ORCID: 0000-0002-6236-338X

Jochen Rössler (J)

Division of Pediatric Hematology and Oncology, Department of Pediatrics, Inselspital - University Hospital of Bern, University of Bern, Bern, Switzerland.
Department of Vascular Medicine, National Reference Centre for Rare Lymphatic and Vascular Diseases, UA11 INSERM - UM IDESP. Campus Santé, Montpellier Cedex 5, France.
ORCID: 0000-0003-4022-4917

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