title: A SWI/SNF-related autism syndrome caused by de novo mutations in ADNP.
abstract: Despite the high heritability of autism spectrum disorders (ASD), characterized by persistent deficits in social communication and interaction and restricted, repetitive patterns of behavior, interests or activities, a genetic diagnosis can be established in only a minority of patients. Known genetic causes include chromosomal aberrations, such as the duplication of the 15q11-13 region, and monogenic causes, as in Rett and fragile-X syndromes. The genetic heterogeneity within ASD is striking, with even the most frequent causes responsible for only 1% of cases at the most. Even with the recent developments in next-generation sequencing, for the large majority of cases no molecular diagnosis can be established. Here, we report ten patients with ASD and other shared clinical characteristics, including intellectual disability and facial dysmorphisms caused by a mutation in ADNP, a transcription factor involved in the SWI/SNF remodeling complex. We estimate this gene to be mutated in at least 0.17% of ASD cases, making it one of the most frequent ASD-associated genes known to date.
authors: Department of Medical Genetics, University of Antwerp, Antwerp, Belgium.
authors: Céline
authors: C
authors: Helsmoortel
authors: 1] Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Institute for Genetic and Metabolic Disease, Radboud University Medical Center, Nijmegen, The Netherlands. [2].
authors: Anneke T
authors: AT
authors: Vulto-van Silfhout
authors: 1] Department of Genome Sciences, University of Washington School of Medicine, Seattle, Washington, USA. [2] Howard Hughes Medical Institute, University of Washington, Seattle, Washington, USA. [3].
authors: Bradley P
authors: BP
authors: Coe
authors: 1] Department of Medical Genetics, University of Antwerp, Antwerp, Belgium. [2] Biomedical informatics research center Antwerpen (Biomina), Department of Mathematics and Computer Science, University of Antwerp, Edegem, Belgium.
authors: Geert
authors: G
authors: Vandeweyer
authors: Department of Medical Genetics, University of Antwerp, Antwerp, Belgium.
authors: Liesbeth
authors: L
authors: Rooms
authors: University Hospital Antwerp, Antwerp, Belgium.
authors: Jenneke
authors: J
authors: van den Ende
authors: Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Institute for Genetic and Metabolic Disease, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Janneke H M
authors: JH
authors: Schuurs-Hoeijmakers
authors: Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Institute for Genetic and Metabolic Disease, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Carlo L
authors: CL
authors: Marcelis
authors: Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Institute for Genetic and Metabolic Disease, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Marjolein H
authors: MH
authors: Willemsen
authors: Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Institute for Genetic and Metabolic Disease, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Lisenka E L M
authors: LE
authors: Vissers
authors: Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Institute for Genetic and Metabolic Disease, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Helger G
authors: HG
authors: Yntema
authors: Department of Genetic Medicine, Westmead Hospital, Sydney, Australia.
authors: Madhura
authors: M
authors: Bakshi
authors: Department of Clinical Genetics, Children's Hospital at Westmead, Westmead, Australia.
authors: Meredith
authors: M
authors: Wilson
authors: 1] Department of Genome Sciences, University of Washington School of Medicine, Seattle, Washington, USA. [2] Howard Hughes Medical Institute, University of Washington, Seattle, Washington, USA.
authors: Kali T
authors: KT
authors: Witherspoon
authors: Clinical Genetics Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
authors: Helena
authors: H
authors: Malmgren
authors: Clinical Genetics Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
authors: Ann
authors: A
authors: Nordgren
authors: Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
authors: Göran
authors: G
authors: Annerén
authors: 1] Unit of Neurology, I.R.C.C.S. Associazione Oasi Maria Santissima, Troina, Italy. [2] Medical Genetics, University of Catania, Catania, Italy.
authors: Marco
authors: M
authors: Fichera
authors: Laboratory of Cytogenetics, I.R.C.C.S. Associazione Oasi Maria Santissima, Troina, Italy.
authors: Paolo
authors: P
authors: Bosco
authors: Unit of Pediatrics and Medical Genetics, I.R.C.C.S. Associazione Oasi Maria Santissima, Troina, Italy.
authors: Corrado
authors: C
authors: Romano
authors: 1] Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Institute for Genetic and Metabolic Disease, Radboud University Medical Center, Nijmegen, The Netherlands. [2] Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Bert B A
authors: BB
authors: de Vries
authors: 1] Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Institute for Genetic and Metabolic Disease, Radboud University Medical Center, Nijmegen, The Netherlands. [2] Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Tjitske
authors: T
authors: Kleefstra
authors: Department of Medical Genetics, University of Antwerp, Antwerp, Belgium.
authors: R Frank
authors: RF
authors: Kooy
authors: 1] Department of Genome Sciences, University of Washington School of Medicine, Seattle, Washington, USA. [2] Howard Hughes Medical Institute, University of Washington, Seattle, Washington, USA.
authors: Evan E
authors: EE
authors: Eichler
authors: 1] Department of Medical Genetics, University of Antwerp, Antwerp, Belgium. [2] University Hospital Antwerp, Antwerp, Belgium.
authors: Nathalie
authors: N
authors: Van der Aa
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D001483:Base Sequence; D002659:Child Development Disorders, Pervasive / Q000235:genetics*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D018389:Codon, Nonsense / Q000235:genetics; D059472:Exome / Q000235:genetics; D016368:Frameshift Mutation / Q000235:genetics; D040461:Gene Components; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C492178:ADNP protein, human; D002868:Chromosomal Proteins, Non-Histone; D018389:Codon, Nonsense; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; C445179:SWI-SNF-B chromatin-remodeling complex; D014157:Transcription Factors