High-resolution chromosomal microarray analysis for copy-number variations in high-functioning autism reveals large aberration typical for intellectual disability.

Autor: Werling AM; Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Wagistrasse 12, 8952, Schlieren, Switzerland.; Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Neumuensterallee 9, 8032, Zurich, Switzerland., Grünblatt E; Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Wagistrasse 12, 8952, Schlieren, Switzerland. edna.gruenblatt@kjpd.uzh.ch.; Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zurich, Switzerland. edna.gruenblatt@kjpd.uzh.ch.; Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland. edna.gruenblatt@kjpd.uzh.ch.; Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Neumuensterallee 9, 8032, Zurich, Switzerland. edna.gruenblatt@kjpd.uzh.ch., Oneda B; Institute of Medical Genetics, University of Zurich, Zurich-Schlieren, Switzerland., Bobrowski E; Isar-Amper-Hospital Taufkirchen, Psychiatry, Psychotherapy and Psychosomatics, Taufkirchen (Vils), Germany., Gundelfinger R; Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Wagistrasse 12, 8952, Schlieren, Switzerland., Taurines R; Center of Mental Health, Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Würzburg, Germany., Romanos M; Center of Mental Health, Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Würzburg, Germany., Rauch A; Institute of Medical Genetics, University of Zurich, Zurich-Schlieren, Switzerland.; Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zurich, Switzerland.; Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland., Walitza S; Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Wagistrasse 12, 8952, Schlieren, Switzerland. susanne.walitza@puk.zh.ch.; Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zurich, Switzerland. susanne.walitza@puk.zh.ch.; Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland. susanne.walitza@puk.zh.ch.; Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Neumuensterallee 9, 8032, Zurich, Switzerland. susanne.walitza@puk.zh.ch.
Jazyk: angličtina
Zdroj: Journal of neural transmission (Vienna, Austria : 1996) [J Neural Transm (Vienna)] 2020 Jan; Vol. 127 (1), pp. 81-94. Date of Electronic Publication: 2019 Dec 14.
DOI: 10.1007/s00702-019-02114-9
Abstrakt: Copy-number variants (CNVs), in particular rare, small and large ones (< 1% frequency) and those encompassing brain-related genes, have been shown to be associated with neurodevelopmental disorders like autism spectrum disorders (ASDs), attention deficit hyperactivity disorder (ADHD), and intellectual disability (ID). However, the vast majority of CNV findings lack specificity with respect to autistic or developmental-delay phenotypes. Therefore, the aim of the study was to investigate the size and frequency of CNVs in high-functioning ASD (HFA) without ID compared with a random population sample and with published findings in ASD and ID. To investigate the role of CNVs for the "core symptoms" of high-functioning autism, we included in the present exploratory study only patients with HFA without ID. The aim was to test whether HFA have similar large rare (> 1 Mb) CNVs as reported in ASD and ID. We performed high-resolution chromosomal microarray analysis in 108 children and adolescents with HFA without ID. There was no significant difference in the overall number of rare CNVs compared to 124 random population samples. However, patients with HFA carried significantly more frequently CNVs containing brain-related genes. Surprisingly, six HFA patients carried very large CNVs known to be typically present in ID. Our findings provide new evidence that not only small, but also large CNVs affecting several key genes contribute to the genetic etiology/risk of HFA without affecting their intellectual ability.
Databáze: MEDLINE
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