caa a22 4500 445364696 CHVBK 20180317142926.0 cr unu---uuuuu 170323e20111101xx s 000 0 eng 10.1007/s10048-011-0297-2 doi (NATIONALLICENCE)springer-10.1007/s10048-011-0297-2 Social responsiveness scale-aided analysis of the clinical impact of copy number variations in autism [Elektronische Daten] [Emma van Daalen, Chantal Kemner, Nienke Verbeek, Bert van der Zwaag, Trijnie Dijkhuizen, Patrick Rump, Renske Houben, Ruben van ‘t Slot, Maretha de Jonge, Wouter Staal, Frits Beemer, Jacob Vorstman, J. Burbach, Hans van Amstel, Ron Hochstenbach, Eva Brilstra, Martin Poot] Recent array-based studies have detected a wealth of copy number variations (CNVs) in patients with autism spectrum disorders (ASD). Since CNVs also occur in healthy individuals, their contributions to the patient's phenotype remain largely unclear. In a cohort of children with symptoms of ASD, diagnosis of the index patient using ADOS-G and ADI-R was performed, and the Social Responsiveness Scale (SRS) was administered to the index patients, both parents, and all available siblings. CNVs were identified using SNP arrays and confirmed by FISH or array CGH. To evaluate the clinical significance of CNVs, we analyzed three families with multiple affected children (multiplex) and six families with a single affected child (simplex) in which at least one child carried a CNV with a brain-transcribed gene. CNVs containing genes that participate in pathways previously implicated in ASD, such as the phosphoinositol signaling pathway (PIK3CA, GIRDIN), contactin-based networks of cell communication (CNTN6), and microcephalin (MCPH1) were found not to co-segregate with ASD phenotypes. In one family, a loss of CNTN5 co-segregated with disease. This indicates that most CNVs may by themselves not be sufficient to cause ASD, but still may contribute to the phenotype by additive or epistatic interactions with inherited (transmitted) mutations or non-genetic factors. Our study extends the scope of genome-wide CNV profiling beyond de novo CNVs in sporadic patients and may aid in uncovering missing heritability in genome-wide screening studies of complex psychiatric disorders. The Author(s), 2011 Autism nationallicence Social Responsiveness Scale (SRS) nationallicence SNP array-based CNV profiling nationallicence Gene prioritization nationallicence Phosphoinositol signaling nationallicence Contactin genes nationallicence van Daalen Emma Department of Child and Adolescent Psychiatry, University Medical Centre, Utrecht, The Netherlands aut Kemner Chantal Department of Child and Adolescent Psychiatry, University Medical Centre, Utrecht, The Netherlands aut Verbeek Nienke Department of Medical Genetics, University Medical Centre, P.O. Box 85090, 3508 AB, Utrecht, The Netherlands aut van der Zwaag Bert Department of Medical Genetics, University Medical Centre, P.O. Box 85090, 3508 AB, Utrecht, The Netherlands aut Dijkhuizen Trijnie Department of Genetics, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands aut Rump Patrick Department of Genetics, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands aut Houben Renske Department of Child and Adolescent Psychiatry, University Medical Centre, Utrecht, The Netherlands aut van ‘t Slot Ruben Department of Medical Genetics, University Medical Centre, P.O. Box 85090, 3508 AB, Utrecht, The Netherlands aut de Jonge Maretha Department of Child and Adolescent Psychiatry, University Medical Centre, Utrecht, The Netherlands aut Staal Wouter Department of Child and Adolescent Psychiatry, University Medical Centre, Utrecht, The Netherlands aut Beemer Frits Department of Medical Genetics, University Medical Centre, P.O. Box 85090, 3508 AB, Utrecht, The Netherlands aut Vorstman Jacob Department of Child and Adolescent Psychiatry, University Medical Centre, Utrecht, The Netherlands aut Burbach J. Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Centre, Utrecht, The Netherlands aut van Amstel Hans Department of Medical Genetics, University Medical Centre, P.O. Box 85090, 3508 AB, Utrecht, The Netherlands aut Hochstenbach Ron Department of Medical Genetics, University Medical Centre, P.O. Box 85090, 3508 AB, Utrecht, The Netherlands aut Brilstra Eva Department of Medical Genetics, University Medical Centre, P.O. Box 85090, 3508 AB, Utrecht, The Netherlands aut Poot Martin Department of Medical Genetics, University Medical Centre, P.O. Box 85090, 3508 AB, Utrecht, The Netherlands aut neurogenetics Springer-Verlag 12/4(2011-11-01), 315-323 1364-6745 12:4<315 2011 12 10048 https://doi.org/10.1007/s10048-011-0297-2 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10048-011-0297-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- van Daalen Emma Department of Child and Adolescent Psychiatry, University Medical Centre, Utrecht, The Netherlands aut NATIONALLICENCE 700 1- Kemner Chantal Department of Child and Adolescent Psychiatry, University Medical Centre, Utrecht, The Netherlands aut NATIONALLICENCE 700 1- Verbeek Nienke Department of Medical Genetics, University Medical Centre, P.O. Box 85090, 3508 AB, Utrecht, The Netherlands aut NATIONALLICENCE 700 1- van der Zwaag Bert Department of Medical Genetics, University Medical Centre, P.O. Box 85090, 3508 AB, Utrecht, The Netherlands aut NATIONALLICENCE 700 1- Dijkhuizen Trijnie Department of Genetics, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands aut NATIONALLICENCE 700 1- Rump Patrick Department of Genetics, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands aut NATIONALLICENCE 700 1- Houben Renske Department of Child and Adolescent Psychiatry, University Medical Centre, Utrecht, The Netherlands aut NATIONALLICENCE 700 1- van ‘t Slot Ruben Department of Medical Genetics, University Medical Centre, P.O. Box 85090, 3508 AB, Utrecht, The Netherlands aut NATIONALLICENCE 700 1- de Jonge Maretha Department of Child and Adolescent Psychiatry, University Medical Centre, Utrecht, The Netherlands aut NATIONALLICENCE 700 1- Staal Wouter Department of Child and Adolescent Psychiatry, University Medical Centre, Utrecht, The Netherlands aut NATIONALLICENCE 700 1- Beemer Frits Department of Medical Genetics, University Medical Centre, P.O. Box 85090, 3508 AB, Utrecht, The Netherlands aut NATIONALLICENCE 700 1- Vorstman Jacob Department of Child and Adolescent Psychiatry, University Medical Centre, Utrecht, The Netherlands aut NATIONALLICENCE 700 1- Burbach J. Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Centre, Utrecht, The Netherlands aut NATIONALLICENCE 700 1- van Amstel Hans Department of Medical Genetics, University Medical Centre, P.O. Box 85090, 3508 AB, Utrecht, The Netherlands aut NATIONALLICENCE 700 1- Hochstenbach Ron Department of Medical Genetics, University Medical Centre, P.O. Box 85090, 3508 AB, Utrecht, The Netherlands aut NATIONALLICENCE 700 1- Brilstra Eva Department of Medical Genetics, University Medical Centre, P.O. Box 85090, 3508 AB, Utrecht, The Netherlands aut NATIONALLICENCE 700 1- Poot Martin Department of Medical Genetics, University Medical Centre, P.O. Box 85090, 3508 AB, Utrecht, The Netherlands aut NATIONALLICENCE 773 0- neurogenetics Springer-Verlag 12/4(2011-11-01), 315-323 1364-6745 12:4<315 2011 12 10048 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer