ArticleJCI insight2019
Genotype correlates with clinical severity in PIK3CA-associated lymphatic malformations.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 2 syntheses or guidelines pooled it, 69 citations in OpenAlex.
- Molecular-genetic mechanisms of cerebral arteriovenous malformations: A systematic review of germline, somatic and experimental evidence.Neurosurgical review · 2026Pooled it
- Medical Therapies for Pediatric Lymphatic Malformations: A Systematic Review.Journal of cutaneous medicine and surgeryPooled it
- Multidisciplinary management of pediatric head and neck lymphatic malformations: a 10-year single-institution experience.International journal of pediatric otorhinolaryngology · 2026Article
- Somatic Genetic Testing Provides Diagnosis of Verrucous Venous Malformation in an Individual with Discrepant Radiology, Pathology, and Clinical Findings.Journal of vascular anomalies · 2025Article
- Multiple Genomic Technologies Validate Rare Novel Variant and Direct Medical Care in Vascular Anomalies.American journal of medical genetics. Part A · 2025Article
- Dysfunctional mechanotransduction regulates the progression of PIK3CA-driven vascular malformations.APL bioengineering · 2025Article
- Dysfunctional mechanotransduction regulates the progression of PIK3CA-driven vascular malformations.bioRxiv : the preprint server for biology · 2024Article
- A multi-step approach to overcome challenges in the management of head and neck lymphatic malformations, and response to treatment.Orphanet journal of rare diseases · 2024Article
- Lymphatic malformations: mechanistic insights and evolving therapeutic frontiers.The Journal of clinical investigation · 2024Review
- The development of early human lymphatic vessels as characterized by lymphatic endothelial markers.The EMBO journal · 2024Article
- Updates in Genetic Testing for Head and Neck Vascular Anomalies.Oral and maxillofacial surgery clinics of North America · 2024Review
- Uncovering somatic mosaic variants ofFrontiers in genetics · 2024Article
- Microcystic lymphatic malformations in Turner syndrome are due to somatic mosaicism of PIK3CA.American journal of medical genetics. Part A · 2024Article
- Targeted next-generation sequencing for detection of PIK3CA mutations in archival tissues from patients with Klippel-Trenaunay syndrome in an Asian population : List the full names and institutional addresses for all authors.Orphanet journal of rare diseases · 2023Article
- Somatic mutation spectrum of a Chinese cohort of pediatrics with vascular malformations.Orphanet journal of rare diseases · 2023Article
- Delineation of the phenotypes and genotypes of facial infiltrating lipomatosis associated with PIK3CA mutations.Orphanet journal of rare diseases · 2023Article
- French national diagnosis and care protocol (PNDS, protocole national de diagnostic et de soins): cystic lymphatic malformations.Orphanet journal of rare diseases · 2023Review
- Primary targeted medical therapy for management of bilateral head and neck lymphatic malformations in infants.International journal of pediatric otorhinolaryngology · 2023Article
- Alpelisib for the treatment of PIK3CA-related head and neck lymphatic malformations and overgrowth.Genetics in medicine : official journal of the American College of Medical Genetics · 2022Article
- Profiling PI3K-AKT-MTOR variants in focal brain malformations reveals new insights for diagnostic care.Brain : a journal of neurology · 2022Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Lymphatic malformations (LMs) are congenital, nonneoplastic vascular malformations associated with postzygotic activating PIK3CA mutations. The mutation spectrum within LMs is narrow, with the majority having 1 of 3 hotspot mutations. Despite this relative genetic homogeneity, clinical presentations differ dramatically. We used molecular inversion probes and droplet digital polymerase chain reaction to perform deep, targeted sequencing of PIK3CA in 271 affected and unaffected tissue samples from 81 individuals with isolated LMs and retrospectively collected clinical data. Pathogenic PIK3CA mutations were identified in affected LM tissue in 64 individuals (79%) with isolated LMs, with variant allele fractions (VAFs) ranging from 0.1% to 13%. Initial analyses revealed no correlation between VAF and phenotype variables. Recognizing that different mutations activate PI3K to varying degrees, we developed a metric, the genotype-adjusted VAF (GVAF), to account for differences in mutation strength, and found significantly higher GVAFs in LMs with more severe clinical characteristics including orofacial location or microcystic structure. In addition to providing insight into LM pathogenesis, we believe GVAF may have broad applicability for genotype-phenotype analyses in mosaic disorders.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.