Variants of human PTEN linked to somatic cancers and disorders on the autism spectrum are shown to be impaired in their conformational stability, catalytic activity, or both.
Exome sequencing of the family also identified a rare inherited variant predicted to disrupt splicing of TPTE / PTEN2, a PTEN homologue, which may likewise contribute to both macrocephaly and autism risk.
Especially useful would be an algorithm for predicting the impact of nonsynonymous single-nucleotide polymorphisms in the gene for PTEN, a protein that is implicated in most human cancers and connected to germline disorders that include autism.
A novel mutation in the PTEN gene was identified in a 16-year-old girl with autism, mental retardation, language delay, extreme macrocephaly (+4.7SD) with a prominent forehead, and digital minor anomalies.
Conformational Dynamics and Allosteric Regulation Landscapes of Germline PTEN Mutations Associated with Autism Compared to Those Associated with Cancer.
Our results lend insight into distinctive structural effects of germline PTEN mutations associated with PTEN-ASD vs. those associated with PTEN-cancer, potentially aiding in identification of the shared and separate molecular features that contribute to autism or cancer, thus, providing a deeper understanding of genotype-phenotype relationships for germline PTEN mutations.
To investigate PTEN's role during neurodevelopment and its implication for autism, several conditional <i>Pten</i> knockout mouse models have been generated.
Phosphatase and tensin homolog on chromosome 10 (PTEN) is a tumor suppressor and autism-associated gene that exerts an important influence over neuronal structure and function during development.