title: The transcriptional regulator ADNP links the BAF (SWI/SNF) complexes with autism.
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.
authors.forename: Geert
authors.initials: G
authors.lastname: Vandeweyer
authors.forename: Céline
authors.initials: C
authors.lastname: Helsmoortel
authors.forename: Anke
authors.initials: A
authors.lastname: Van Dijck
authors.forename: Anneke T
authors.initials: AT
authors.lastname: Vulto-van Silfhout
authors.forename: Bradley P
authors.initials: BP
authors.lastname: Coe
authors.forename: Raphael
authors.initials: R
authors.lastname: Bernier
authors.forename: Jennifer
authors.initials: J
authors.lastname: Gerdts
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Rooms
authors.forename: Jenneke
authors.initials: J
authors.lastname: van den Ende
authors.forename: Madhura
authors.initials: M
authors.lastname: Bakshi
authors.forename: Meredith
authors.initials: M
authors.lastname: Wilson
authors.forename: Ann
authors.initials: A
authors.lastname: Nordgren
authors.forename: Laura G
authors.initials: LG
authors.lastname: Hendon
authors.forename: Omar A
authors.initials: OA
authors.lastname: Abdulrahman
authors.forename: Corrado
authors.initials: C
authors.lastname: Romano
authors.forename: Bert B A
authors.initials: BB
authors.lastname: de Vries
authors.forename: Tjitske
authors.initials: T
authors.lastname: Kleefstra
authors.forename: Evan E
authors.initials: EE
authors.lastname: Eichler
authors.forename: Nathalie
authors.initials: N
authors.lastname: Van der Aa
authors.forename: R Frank
authors.initials: RF
authors.lastname: Kooy
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D000818:Animals; D001321:Autistic Disorder / Q000209:etiology / Q000235:genetics*; D002675:Child, Preschool; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism; D005145:Face / Q000002:abnormalities; D006228:Hand Deformities, Congenital / Q000235:genetics; D057895:Haploinsufficiency / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics; D018345:Mice, Knockout; D008844:Micrognathism / Q000235:genetics; D009154:Mutation; D009333:Neck / Q000002:abnormalities; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: C492178:ADNP protein, human; C117632:Adnp protein, mouse; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D009842:Oligopeptides; C084011:SMARCA2 protein, human; D014157:Transcription Factors; C084108:SMARCA4 protein, human; D004265:DNA Helicases; C425904:davunetide
keywords: ADNP; BAF complexes; SWI/SNF; autism