TY - JOUR
T1 - The transcriptional regulator ADNP links the BAF (SWI/SNF) complexes with Autism
AU - Vandeweyer, Geert
AU - Helsmoortel, Céline
AU - VanDijck, Anke
AU - Vulto-Van Silfhout, Anneke T.
AU - Coe, Bradley P.
AU - Bernier, Raphael
AU - Gerdts, Jennifer
AU - Rooms, Liesbeth
AU - Van Den Ende, Jenneke
AU - Bakshi, Madhura
AU - Wilson, Meredith
AU - Nordgren, Ann
AU - Hendon, Laura G.
AU - Abdulrahman, Omar A.
AU - Romano, Corrado
AU - De Vries, Bert B.A.
AU - Kleefstra, Tjitske
AU - Eichler, Evan E.
AU - Van Der Aa, Nathalie
AU - Frank Kooy, R.
N1 - Publisher Copyright:
© 2014 Wiley Periodicals, Inc.
PY - 2014/9
Y1 - 2014/9
N2 - 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.
AB - 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.
KW - ADNP
KW - Autism
KW - BAF complexes
KW - SWI/SNF
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U2 - 10.1002/ajmg.c.31413
DO - 10.1002/ajmg.c.31413
M3 - Article
C2 - 25169753
AN - SCOPUS:84908641727
VL - 166
SP - 315
EP - 326
JO - American Journal of Medical Genetics, Part C: Seminars in Medical Genetics
JF - American Journal of Medical Genetics, Part C: Seminars in Medical Genetics
SN - 1552-4868
IS - 3
ER -