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The transcriptional regulator ADNP links the BAF (SWI/SNF) complexes with autism
Author(s) -
Vandeweyer Geert,
Helsmoortel Céline,
Van Dijck Anke,
Vultovan Silfhout Anneke T.,
Coe Bradley P.,
Bernier Raphael,
Gerdts Jennifer,
Rooms Liesbeth,
van den Ende Jenneke,
Bakshi Madhura,
Wilson Meredith,
Nordgren Ann,
Hendon Laura G.,
Abdulrahman Omar A.,
Romano Corrado,
de Vries Bert B.A.,
Kleefstra Tjitske,
Eichler Evan E.,
Van der Aa Nathalie,
Kooy R. Frank
Publication year - 2014
Publication title -
american journal of medical genetics part c: seminars in medical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.419
H-Index - 101
eISSN - 1552-4876
pISSN - 1552-4868
DOI - 10.1002/ajmg.c.31413
Subject(s) - regulator , swi/snf , transcriptional regulation , master regulator , autism , chemistry , biology , microbiology and biotechnology , genetics , psychology , gene , transcription factor , developmental psychology , chromatin remodeling
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. © 2014 Wiley Periodicals, Inc.