Distinguishing between PTEN clinical phenotypes through mutation analysis

Abstract

Phosphate and tensin homolog on chromosome ten (PTEN) germline mutations are associated with an overarching condition known as PTEN hamartoma tumor syndrome. Clinical phenotypes associated with this syndrome range from macrocephaly and autism spectrum disorder to Cowden syndrome, which manifests as multiple noncancerous tumor-like growths (hamartomas), and an increased predisposition to certain cancers. It is unclear, however, the basis by which mutations might lead to these very diverse phenotypic outcomes. Here we show that, by considering the molecular consequences of mutations in PTEN on protein structure and function, we can accurately distinguish PTEN mutations exhibiting different phe..