Article Text
Abstract
Background Germline mutations in the phosphatase PTEN are associated with diverse human pathologies, including tumour susceptibility, developmental abnormalities and autism, but any genotype-phenotype relationships are poorly understood.
Methods We have studied the functional consequences of seven PTEN mutations identified in patients diagnosed with autism and macrocephaly and five mutations from severe tumour bearing sufferers of PTEN hamartoma tumour syndrome (PHTS).
Results All seven autism-associated PTEN mutants investigated retained the ability to suppress cellular AKT signalling, although five were highly unstable. Observed effects on AKT also correlated with the ability to suppress soma size and the length and density of dendritic spines in primary neurons. Conversely, all five PTEN mutations from severe cases of PHTS appeared to directly and strongly disrupt the ability to inhibit AKT signalling.
Conclusions Our work implies that alleles causing incomplete loss of PTEN function are more commonly linked to autism than to severe PHTS cases.
- Cancer: breast
- Neurosciences
- Cell biology
This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/
Statistics from Altmetric.com
Supplementary materials
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Files in this Data Supplement:
- Data supplement 1 - Online supplement