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.
| Original language | English |
|---|---|
| Pages (from-to) | 128-134 |
| Number of pages | 7 |
| Journal | Journal of Medical Genetics |
| Volume | 52 |
| Issue number | 2 |
| Early online date | 19 Dec 2014 |
| DOIs | |
| Publication status | Published - Feb 2015 |
Keywords
- LHERMITTE-DUCLOS-DISEASE
- BANNAYAN-ZONANA-SYNDROME
- SPECTRUM DISORDERS
- COWDEN-SYNDROME
- GERMLINE MUTATION
- SOMA SIZE
- MICE
- SUPPRESSOR
- FAMILY
- CANCER
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Nicholas R. Leslie
- School of Engineering & Physical Sciences - Professor
- School of Engineering & Physical Sciences, Institute of Biological Chemistry, Biophysics and Bioengineering - Professor
- School of Engineering & Physical Sciences, Institute of Chemical Sciences - Professor
Person: Academic (Research & Teaching)