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ORIGINAL RESEARCH article

Front. Genet.
Sec. Human and Medical Genomics
Volume 15 - 2024 | doi: 10.3389/fgene.2024.1484651
This article is part of the Research Topic Application of Next-Generation Sequencing in Clinical Settings View all 6 articles

Uncovering somatic mosaic variants of PIK3CA-Related Overgrowth Disorders: Three cases with different clinical presentations

Provisionally accepted
Mikk Tooming Mikk Tooming 1,2*Piret Mertsina Piret Mertsina 2Tiina Kahre Tiina Kahre 1,2Rita Teek Rita Teek 2Inga Vainumäe Inga Vainumäe 3,4Stella Lilles Stella Lilles 3,4Monica Wojcik Monica Wojcik 5,6,7Pilvi Ilves Pilvi Ilves 8,9Katrin Õunap Katrin Õunap 1,2
  • 1 Genetics and Personalized Medicine Clinic, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia
  • 2 Genetics and Personalized Medicine Clinic, Tartu University Hospital, Tartu, Estonia
  • 3 Children's Clinic, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia
  • 4 Children's Clinic, Tartu University Hospital, Tartu, Estonia
  • 5 Divisions of Newborn Medicine and Genetics and Genomics, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, United States
  • 6 Manton Center for Orphan Disease Research, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, United States
  • 7 Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard, Cambridge, United States
  • 8 Department of Radiology, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia
  • 9 Radiology Clinic, Tartu University Hospital, Tartu, Estonia

The final, formatted version of the article will be published soon.

    PIK3CA-related disorders (PRD, OMIM: *171834) are genetic disorders resulting from pathogenic somatic mosaic variants in PIK3CA, which encodes a protein crucial in regulating cell growth and division. PRD typically manifest during the post-zygotic phase and can give rise to a broad spectrum of overgrowth and vascular malformations affecting different body regions. Conventional diagnostic methods face challenges in detecting and confirming pathogenic PIK3CA gene variants due to the mosaic nature and limited accessibility of affected tissues. We describe a cohort of individuals with PRD in order to underscore the diagnostic challenges posed by somatic mosaicism in PRD. Our findings advocate for adopting comprehensive genomic profiling to meticulously evaluate all potentially pathogenic gene variants associated with PRD in affected individuals and their corresponding tissues, improving patient care and management.

    Keywords: PIK3CA-related overgrowth syndrome, PIK3CA somatic mosaic variants, Overgrowth syndrome, next-generation sequencing-based genomic profiling, PIK3CA, PIK3CA somatic mutation

    Received: 22 Aug 2024; Accepted: 12 Dec 2024.

    Copyright: © 2024 Tooming, Mertsina, Kahre, Teek, Vainumäe, Lilles, Wojcik, Ilves and Õunap. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Mikk Tooming, Genetics and Personalized Medicine Clinic, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.