Table 1.

Molecular Genetic Testing Used in PIK3CA-Related Overgrowth Spectrum

Gene 1MethodProportion of Probands with a Pathogenic Variant 2 Detectable by Method
PIK3CA Sequence analysis 3, 4100% 5
Gene-targeted deletion/duplication analysis 6None reported 7
1.
2.

See Molecular Genetics for information on variants detected in this gene.

3.

Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include missense, nonsense, and splice site variants and small intragenic deletions/insertions; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.

4.

The choice of method for somatic PIK3CA variant detection (see Molecular Genetics) depends on several factors. Several manufacturers have developed PCR-based assays for detection of specific PIK3CA variants commonly found in cancers, and many of these variants have also been found in individuals with PROS as well. The data suggest that while there are mutational hot spots (e.g., PIK3CA codons 542, 545, and 1047), there are a substantial number of rare pathogenic variants.

5.

Because most affected individuals have a somatic mosaic PIK3CA pathogenic variant, the actual detection rate depends on the type of sample provided and the molecular genetic testing method used.

6.

Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.

7.

The pathogenic variants observed in PROS have all been associated with gain of function; thus, partial or whole PIK3CA deletions and duplications are not likely to lead to this phenotype.

From: PIK3CA-Related Overgrowth Spectrum

Cover of GeneReviews®
GeneReviews® [Internet].
Adam MP, Feldman J, Mirzaa GM, et al., editors.
Seattle (WA): University of Washington, Seattle; 1993-2024.
Copyright © 1993-2024, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.

GeneReviews® chapters are owned by the University of Washington. Permission is hereby granted to reproduce, distribute, and translate copies of content materials for noncommercial research purposes only, provided that (i) credit for source (http://www.genereviews.org/) and copyright (© 1993-2024 University of Washington) are included with each copy; (ii) a link to the original material is provided whenever the material is published elsewhere on the Web; and (iii) reproducers, distributors, and/or translators comply with the GeneReviews® Copyright Notice and Usage Disclaimer. No further modifications are allowed. For clarity, excerpts of GeneReviews chapters for use in lab reports and clinic notes are a permitted use.

For more information, see the GeneReviews® Copyright Notice and Usage Disclaimer.

For questions regarding permissions or whether a specified use is allowed, contact: ude.wu@tssamda.

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.