PTENencodes a phosphatase that antagonizes PI3K/AKT signaling and plays a key role in cell growth, proliferation and survival. Pathogenic variants are usually loss-of-function variants, including nonsense, frameshift, splice-site, and missense variants affecting critical residues; intragenic deletions and larger genomic rearrangements may also occur. The disease mechanism is haploinsufficiency.
Diagnostic testing includes sequencing of the coding region and splice sites, with deletion/duplication analysis when sequencing is negative. In selected cases, testing of non-coding regions may be considered if clinical suspicion remains high.
PTEN