Title
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The transcriptional regulator ADNP links the BAF (SWI/SNF) complexes with autism
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Author
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Abstract
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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. (c) 2014 Wiley Periodicals, Inc. |
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Language
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English
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Source (journal)
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American journal of medical genetics: part C: seminars in medical genetics. - Bognor Regis
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Publication
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Bognor Regis
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2014
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ISSN
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1552-4868
[print]
1552-4876
[online]
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DOI
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10.1002/AJMG.C.31413
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Volume/pages
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166
:3
(2014)
, p. 315-326
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ISI
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000342343200008
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Pubmed ID
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25169753
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Full text (Publisher's DOI)
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Full text (open access)
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