Uncovering somatic mosaic variants of PIK3CA-related overgrowth disorders - three cases with different clinical presentations.

IF 2.8 3区生物学 Q2 GENETICS & HEREDITY Frontiers in Genetics Pub Date : 2025-01-13 eCollection Date: 2024-01-01 DOI:10.3389/fgene.2024.1484651

M Tooming, P Mertsina, T Kahre, R Teek, I Vainumäe, S Lilles, M H Wojcik, P Ilves, K Õunap

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Abstract

Introduction: PIK3CA 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.

Methods: Conventional 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.

Results: Our 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.

Discussion: Our 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.

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揭示与pik3ca相关的过度生长疾病的体细胞镶嵌变异-三个不同临床表现的病例。

PIK3CA相关疾病（PRD, OMIM: *171834）是由PIK3CA基因的致病性体细胞镶嵌变异引起的遗传性疾病，该基因编码一种对调节细胞生长和分裂至关重要的蛋白质。PRD通常表现在受精卵后阶段，导致广泛的过度生长和血管畸形，影响身体的各个区域。方法：由于这些疾病的马赛克性质和受影响组织的有限可及性，传统的诊断方法难以检测和确认致病性PIK3CA基因变异。在这项研究中，我们对一组患有PRD的个体进行了全面的基因组分析，以解决这些诊断挑战。结果：我们的分析揭示了PRD中体细胞嵌合现象所带来的重大诊断挑战。全面的基因组图谱允许对受影响个体及其相应组织中潜在致病基因变异进行细致的评估。讨论：我们的研究结果提倡在临床实践中采用全面的基因组图谱来改善PRD的检测和管理。这种方法可以通过提供更准确的诊断和更好地了解PRD的遗传基础来加强患者护理。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Frontiers in Genetics Biochemistry, Genetics and Molecular Biology-Molecular Medicine

CiteScore

5.50

自引率

8.10%

发文量

3491

审稿时长

14 weeks

期刊介绍： Frontiers in Genetics publishes rigorously peer-reviewed research on genes and genomes relating to all the domains of life, from humans to plants to livestock and other model organisms. Led by an outstanding Editorial Board of the world’s leading experts, this multidisciplinary, open-access journal is at the forefront of communicating cutting-edge research to researchers, academics, clinicians, policy makers and the public. The study of inheritance and the impact of the genome on various biological processes is well documented. However, the majority of discoveries are still to come. A new era is seeing major developments in the function and variability of the genome, the use of genetic and genomic tools and the analysis of the genetic basis of various biological phenomena.