The transcriptional regulator ADNP links the BAF (SWI/SNF) complexes with autism.
Am J Med Genet C Semin Med Genet
; 166C(3): 315-26, 2014 Sep.
Article
em En
| MEDLINE
| ID: mdl-25169753
ABSTRACT
Mutations in ADNP were recently identified as a frequent cause of syndromic autism, characterized by deficits in social communication and interaction and restricted, repetitive behavioral patterns. Based on its functional domains, ADNP is a presumed transcription factor. The gene interacts closely with the SWI/SNF complex by direct and experimentally verified binding of its C-terminus to three of its core components. A detailed and systematic clinical assessment of the symptoms observed in our patients allows a detailed comparison with the symptoms observed in other SWI/SNF disorders. While the mutational mechanism of the first 10 patients identified suggested a gain of function mechanism, an 11th patient reported here is predicted haploinsufficient. The latter observation may raise hope for therapy, as addition of NAP, a neuroprotective octapeptide named after the first three amino acids of the sequence NAPVSPIQ, has been reported by others to ameliorate some of the cognitive abnormalities observed in a knockout mouse model. It is concluded that detailed clinical and molecular studies on larger cohorts of patients are necessary to establish a better insight in the genotype phenotype correlation and in the mutational mechanism.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transtorno Autístico
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Proteínas de Homeodomínio
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Mutação
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Proteínas do Tecido Nervoso
Tipo de estudo:
Etiology_studies
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Prognostic_studies
Limite:
Animals
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Child, preschool
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Humans
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Infant
Idioma:
En
Revista:
Am J Med Genet C Semin Med Genet
Ano de publicação:
2014
Tipo de documento:
Article