Functionally distinct groups of inherited PTEN mutations in autism and tumour syndromes

77Citations
Citations of this article
122Readers
Mendeley users who have this article in their library.

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.

References Powered by Scopus

Germline transmission and tissue-specific expression of transgenes delivered by lentiviral vectors

1677Citations
N/AReaders
Get full text

The functions and regulation of the PTEN tumour suppressor

1673Citations
N/AReaders
Get full text

Pten Regulates Neuronal Arborization and Social Interaction in Mice

784Citations
N/AReaders
Get full text

Cited by Powered by Scopus

Clinical spectrum and features of activated phosphoinositide 3-kinase δ syndrome: A large patient cohort study

352Citations
N/AReaders
Get full text

Synaptopathology involved in autism spectrum disorder

197Citations
N/AReaders
Get full text

The Clinical Spectrum of PTEN Mutations

168Citations
N/AReaders
Get full text

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Cite

CITATION STYLE

APA

Spinelli, L., Black, F. M., Berg, J. N., Eickholt, B. J., & Leslie, N. R. (2015). Functionally distinct groups of inherited PTEN mutations in autism and tumour syndromes. Journal of Medical Genetics, 52(2), 128–134. https://doi.org/10.1136/jmedgenet-2014-102803

Readers' Seniority

Tooltip

PhD / Post grad / Masters / Doc 50

63%

Researcher 21

26%

Professor / Associate Prof. 8

10%

Lecturer / Post doc 1

1%

Readers' Discipline

Tooltip

Biochemistry, Genetics and Molecular Bi... 30

38%

Agricultural and Biological Sciences 23

29%

Medicine and Dentistry 14

18%

Neuroscience 12

15%

Save time finding and organizing research with Mendeley

Sign up for free