Uncovering somatic mosaic variants of PIK3CA-related overgrowth disorders – three cases with different clinical presentations
IntroductionPIK3CA related disorders (PRD, OMIM: *171834) are genetic disorders resulting from pathogenic somatic mosaic variants in the PIK3CA gene, which encodes a protein crucial for regulating cell growth and division. PRD typically manifest during the post-zygotic phase, leading to a broad spec...
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Frontiers Media S.A.
2025-01-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2024.1484651/full |
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| author | M. Tooming M. Tooming P. Mertsina T. Kahre T. Kahre R. Teek I. Vainumäe I. Vainumäe S. Lilles S. Lilles M. H. Wojcik M. H. Wojcik M. H. Wojcik P. Ilves P. Ilves K. Õunap K. Õunap |
| author_facet | M. Tooming M. Tooming P. Mertsina T. Kahre T. Kahre R. Teek I. Vainumäe I. Vainumäe S. Lilles S. Lilles M. H. Wojcik M. H. Wojcik M. H. Wojcik P. Ilves P. Ilves K. Õunap K. Õunap |
| author_sort | M. Tooming |
| collection | DOAJ |
| description | IntroductionPIK3CA related disorders (PRD, OMIM: *171834) are genetic disorders resulting from pathogenic somatic mosaic variants in the PIK3CA gene, which encodes a protein crucial for regulating cell growth and division. PRD typically manifest during the post-zygotic phase, leading to a broad spectrum of overgrowth and vascular malformations affecting various body regions.MethodsConventional diagnostic methods struggle to detect and confirm pathogenic PIK3CA gene variants due to the mosaic nature of these disorders and the limited accessibility of affected tissues. In this study, we conducted comprehensive genomic profiling on a cohort of individuals with PRD to address these diagnostic challenges.ResultsOur analysis revealed significant diagnostic challenges posed by somatic mosaicism in PRD. The comprehensive genomic profiling allowed for the meticulous evaluation of potentially pathogenic gene variants in affected individuals and their corresponding tissues.DiscussionOur findings advocate for the adoption of comprehensive genomic profiling in clinical practice to improve the detection and management of PRD. This approach can enhance patient care by providing a more accurate diagnosis and better understanding of the genetic underpinnings of PRD. |
| format | Article |
| id | doaj-art-88fbd5386ab9469c92860365e6e6aea2 |
| institution | Kabale University |
| issn | 1664-8021 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj-art-88fbd5386ab9469c92860365e6e6aea22025-01-13T06:10:49ZengFrontiers Media S.A.Frontiers in Genetics1664-80212025-01-011510.3389/fgene.2024.14846511484651Uncovering somatic mosaic variants of PIK3CA-related overgrowth disorders – three cases with different clinical presentationsM. Tooming0M. Tooming1P. Mertsina2T. Kahre3T. Kahre4R. Teek5I. Vainumäe6I. Vainumäe7S. Lilles8S. Lilles9M. H. Wojcik10M. H. Wojcik11M. H. Wojcik12P. Ilves13P. Ilves14K. Õunap15K. Õunap16Genetics and Personalized Medicine Clinic, Institute of Clinical Medicine, University of Tartu, Tartu, EstoniaGenetics and Personalized Medicine Clinic, Tartu University Hospital, Tartu, EstoniaGenetics and Personalized Medicine Clinic, Tartu University Hospital, Tartu, EstoniaGenetics and Personalized Medicine Clinic, Institute of Clinical Medicine, University of Tartu, Tartu, EstoniaGenetics and Personalized Medicine Clinic, Tartu University Hospital, Tartu, EstoniaGenetics and Personalized Medicine Clinic, Tartu University Hospital, Tartu, EstoniaChildren’s Clinic, Institute of Clinical Medicine, University of Tartu, Tartu, EstoniaChildren’s Clinic, Tartu University Hospital, Tartu, EstoniaChildren’s Clinic, Institute of Clinical Medicine, University of Tartu, Tartu, EstoniaChildren’s Clinic, Tartu University Hospital, Tartu, EstoniaDivisions of Newborn Medicine and Genetics and Genomics, Department of Pediatrics, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United StatesManton Center for Orphan Disease Research, Division of Genetics and Genomics, Department of Pediatrics, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United StatesBroad Center for Mendelian Genomics, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, United StatesDepartment of Radiology, Institute of Clinical Medicine, University of Tartu, Tartu, EstoniaRadiology Clinic, Tartu University Hospital, Tartu, EstoniaGenetics and Personalized Medicine Clinic, Institute of Clinical Medicine, University of Tartu, Tartu, EstoniaGenetics and Personalized Medicine Clinic, Tartu University Hospital, Tartu, EstoniaIntroductionPIK3CA related disorders (PRD, OMIM: *171834) are genetic disorders resulting from pathogenic somatic mosaic variants in the PIK3CA gene, which encodes a protein crucial for regulating cell growth and division. PRD typically manifest during the post-zygotic phase, leading to a broad spectrum of overgrowth and vascular malformations affecting various body regions.MethodsConventional diagnostic methods struggle to detect and confirm pathogenic PIK3CA gene variants due to the mosaic nature of these disorders and the limited accessibility of affected tissues. In this study, we conducted comprehensive genomic profiling on a cohort of individuals with PRD to address these diagnostic challenges.ResultsOur analysis revealed significant diagnostic challenges posed by somatic mosaicism in PRD. The comprehensive genomic profiling allowed for the meticulous evaluation of potentially pathogenic gene variants in affected individuals and their corresponding tissues.DiscussionOur findings advocate for the adoption of comprehensive genomic profiling in clinical practice to improve the detection and management of PRD. This approach can enhance patient care by providing a more accurate diagnosis and better understanding of the genetic underpinnings of PRD.https://www.frontiersin.org/articles/10.3389/fgene.2024.1484651/fullPIK3CA-related overgrowth syndromePIK3CA somatic mosaic variantsovergrowth syndromenext-generation sequencing-based genomic profilingPIK3CAPIK3CA somatic mutation |
| spellingShingle | M. Tooming M. Tooming P. Mertsina T. Kahre T. Kahre R. Teek I. Vainumäe I. Vainumäe S. Lilles S. Lilles M. H. Wojcik M. H. Wojcik M. H. Wojcik P. Ilves P. Ilves K. Õunap K. Õunap Uncovering somatic mosaic variants of PIK3CA-related overgrowth disorders – three cases with different clinical presentations Frontiers in Genetics PIK3CA-related overgrowth syndrome PIK3CA somatic mosaic variants overgrowth syndrome next-generation sequencing-based genomic profiling PIK3CA PIK3CA somatic mutation |
| title | Uncovering somatic mosaic variants of PIK3CA-related overgrowth disorders – three cases with different clinical presentations |
| title_full | Uncovering somatic mosaic variants of PIK3CA-related overgrowth disorders – three cases with different clinical presentations |
| title_fullStr | Uncovering somatic mosaic variants of PIK3CA-related overgrowth disorders – three cases with different clinical presentations |
| title_full_unstemmed | Uncovering somatic mosaic variants of PIK3CA-related overgrowth disorders – three cases with different clinical presentations |
| title_short | Uncovering somatic mosaic variants of PIK3CA-related overgrowth disorders – three cases with different clinical presentations |
| title_sort | uncovering somatic mosaic variants of pik3ca related overgrowth disorders three cases with different clinical presentations |
| topic | PIK3CA-related overgrowth syndrome PIK3CA somatic mosaic variants overgrowth syndrome next-generation sequencing-based genomic profiling PIK3CA PIK3CA somatic mutation |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2024.1484651/full |
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