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

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


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.


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.


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.


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.


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

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