The transcriptional regulator ADNP links the BAF (SWI/SNF) complexes with autism.
paper
Cited
Public
- Authors
- Vandeweyer, Geert; Helsmoortel, Céline; Van Dijck, Anke; Vulto-van 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
- Year
- 2014
- Journal
- American journal of medical genetics. Part C, Seminars in medical genetics
- PMID
- 25169753
- DOI
- 10.1002/ajmg.c.31413
- PMCID
- PMC4195434
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.
http://adnpgene.com forms a portal of a collaborative research project to further characterize the phenotype and future development of patients with ADNP mutations.
a: Schematic representation of the ADNP protein. Symbols: previous cases, new case, controls and cases for which expression analysis was performed. b: Amino acid positions of the different domains.
a–f: Patients 1 (a), 2 (b), 4 (c), 5 (d), 6 (e) and 8 (f) at young ages. Note the clinical similarities, including a prominent forehead, a thin upper lip and a broad nasal bridge. Reproduced with permission from Helsmoortel et al., 2004.
First-level interaction partners of ADNP. Data were retrieved from the STRING database and are based on experimental data only [von Mering et al., 2007].
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| Variation in SWI/SNF Chromatin Remodeling Complex Proteins is Associated with Alcohol Dependence and Antisocial Behavior in Human Populations. | 2017 | 28981154 |
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