The transcriptional regulator ADNP links the BAF (SWI/SNF) complexes with Autism

Geert Vandeweyer, Céline Helsmoortel, Anke VanDijck, Anneke T. Vulto-Van Silfhout, Bradley P. Coe, Raphael Bernier, Jennifer Gerdts, Liesbeth Rooms, Jenneke Van Den Ende, Madhura Bakshi, Meredith Wilson, Ann Nordgren, Laura G. Hendon, Omar A. Abdulrahman, Corrado Romano, Bert B.A. De Vries, Tjitske Kleefstra, Evan E. Eichler, Nathalie Van Der Aa, R. Frank Kooy

Research output: Contribution to journalArticle

44 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)315-326
Number of pages12
JournalAmerican Journal of Medical Genetics, Part C: Seminars in Medical Genetics
Volume166
Issue number3
DOIs
StatePublished - 2014

Keywords

  • ADNP
  • Autism
  • BAF complexes
  • SWI/SNF

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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