Functionally distinct groups of inherited PTEN mutations in autism and tumour syndromes.
J Med Genet
; 52(2): 128-34, 2015 Feb.
Article
em En
| MEDLINE
| ID: mdl-25527629
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transtorno Autístico
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Síndrome do Hamartoma Múltiplo
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Predisposição Genética para Doença
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Mutação de Sentido Incorreto
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Padrões de Herança
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PTEN Fosfo-Hidrolase
Limite:
Humans
Idioma:
En
Revista:
J Med Genet
Ano de publicação:
2015
Tipo de documento:
Article