ArticleGenetics in medicine : official journal of the American College of Medical Genetics2021
Somatic PIK3R1 variation as a cause of vascular malformations and overgrowth.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 59 citations in OpenAlex.
- A PMS2-deficient pediatric high-grade glioma with PI3K-pathway mutations and adjacent developmental venous anomaly suggestive of CMMRD.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2026Article
- Vascular malformations: from genetics to therapeutics.EMBO molecular medicine · 2026Review
- Tracing the evolution of sequencing into the era of genomic medicine.Nature reviews. Genetics · 2025Review
- A visual analysis of research hotspots and trends on macrodactyly between 2005 and 2024.Orphanet journal of rare diseases · 2025Article
- Infantile myofibromatosis and capillary malformation of the skin due to PDGFRB mosaicism.Molecular and cellular pediatrics · 2025Review
- Effects and mechanisms of trifolin on attenuating hypertension-induced vascular smooth muscle cell proliferation and collagen deposition in vivo and in vitro.Scientific reports · 2025Article
- Correlation Between PIK3R1 Expression and Cell Growth in Human Breast Cancer Cell Line BT-474 and Clinical Outcomes.World journal of oncology · 2025Article
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- Assessing Protein Surface-Based Scoring for Interpreting Genomic Variants.International journal of molecular sciences · 2024Article
- Paradoxical dominant negative activity of an immunodeficiency-associated activatingbioRxiv : the preprint server for biology · 2024Article
- Defining the transcriptome of PIK3CA-altered cells in a human capillary malformation using single cell long-read sequencing.Scientific reports · 2024Article
- Delineation of the phenotypes and genotypes of PIK3CA-related overgrowth spectrum in East asians.Molecular genetics and genomics : MGG · 2024Article
- Assessment of gene-disease associations and recommendations for genetic testing for somatic variants in vascular anomalies by VASCERN-VASCA.Orphanet journal of rare diseases · 2024Article
- Structural and Dynamic Analyses of Pathogenic Variants inLife (Basel, Switzerland) · 2024Article
- Updates in Genetic Testing for Head and Neck Vascular Anomalies.Oral and maxillofacial surgery clinics of North America · 2024Review
- Association Between theInternational journal of general medicine · 2024Article
- A somatic splice-site variant in PIK3R1 in a patient with vascular overgrowth and low immunoglobulin levels: A case report.Molecular genetics & genomic medicine · 2023Review
- Late-onset Proteus syndrome with cerebriform connective tissue nevus and subsequent development of intraductal papilloma.American journal of medical genetics. Part A · 2022Article
- When, where and which PIK3CA mutations are pathogenic in congenital disorders.Nature cardiovascular research · 2022Review
Corrections and comments
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Authors and funding
23 authors at 14 institutions in 2 countries.
Funding
Abstract
purposeSomatic activating variants in the PI3K-AKT pathway cause vascular malformations with and without overgrowth. We previously reported an individual with capillary and lymphatic malformation harboring a pathogenic somatic variant in PIK3R1, which encodes three PI3K complex regulatory subunits. Here, we investigate PIK3R1 in a large cohort with vascular anomalies and identify an additional 16 individuals with somatic mosaic variants in PIK3R1.
methodsAffected tissue from individuals with vascular lesions and overgrowth recruited from a multisite collaborative network was studied. Next-generation sequencing targeting coding regions of cell-signaling and cancer-associated genes was performed followed by assessment of variant pathogenicity.
resultsThe phenotypic and variant spectrum associated with somatic variation in PIK3R1 is reported herein. Variants occurred in the inter-SH2 or N-terminal SH2 domains of all three PIK3R1 protein products. Phenotypic features overlapped those of the PIK3CA-related overgrowth spectrum (PROS). These overlapping features included mixed vascular malformations, sandal toe gap deformity with macrodactyly, lymphatic malformations, venous ectasias, and overgrowth of soft tissue or bone.
conclusionSomatic PIK3R1 variants sharing attributes with cancer-associated variants cause complex vascular malformations and overgrowth. The PIK3R1-associated phenotypic spectrum overlaps with PROS. These data extend understanding of the diverse phenotypic spectrum attributable to genetic variation in the PI3K-AKT pathway.
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