Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/20800
Title: Recessive variants in ZNF142 cause a complex neurodevelopmental disorder with intellectual disability, speech impairment, seizures, and dystonia.
Authors: Khan, Kamal;Zech, Michael;Morgan, Angela T;Amor, David J;Skorvanek, Matej;Khan, Tahir N;Hildebrand, Michael S;Jackson, Victoria E;Scerri, Thomas S;Coleman, Matthew;Rigbye, Kristin A;Scheffer, Ingrid E;Bahlo, Melanie;Wagner, Matias;Lam, Daniel D;Berutti, Riccardo;Havránková, Petra;Fečíková, Anna;Strom, Tim M;Han, Vladimir;Dosekova, Petra;Gdovinova, Zuzana;Laccone, Franco;Jameel, Muhammad;Mooney, Marie R;Baig, Shahid M;Jech, Robert;Davis, Erica E;Katsanis, Nicholas;Winkelmann, Juliane
Affiliation: Epilepsy Research Centre, Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
Institute of Neurogenomics, Helmholtz Zentrum München, Munich, Germany
Institut für Humangenetik, Technische Universität München, Munich, Germany
Department of Neurology, P.J. Safarik University, Kosice, Slovak Republic
Department of Neurology, University Hospital of L. Pasteur, Kosice, Slovak Republic
Institut für Humangenetik, Technische Universität München, Munich, Germany
Institut für Humangenetik, Helmholtz Zentrum München, Munich, Germany
Human Molecular Genetics Laboratory, Health Biotechnology Division, National Institute for Biotechnology and Genetic Engineering (NIBGE), Faisalabad, Pakistan
Pakistan Institute of Engineering and Applied Sciences (PIEAS), Islamabad, Pakistan
Lehrstuhl für Neurogenetik, Technische Universität München, Munich, Germany
Munich Cluster for Systems Neurology, SyNergy, Munich, Germany
University of Melbourne Department of Paediatrics, Royal Children's Hospital, and Florey and Murdoch Children's Research Institute, Parkville, VIC, Australia
Murdoch Children's Research Institute and University of Melbourne Department of Paediatrics, Royal Children's Hospital, Parkville, Australia
Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, and University of Melbourne Department of Medical Biology and School of Mathematics and Statistics, Parkville, VIC, Australia
Center for Human Disease Modeling, Duke University Medical Center, Durham, NC, USA
Institute of Medical Genetics, Medical School of Vienna, Vienna, Austria
Department of Biological Sciences, National University of Medical Sciences, Rawalpindi, Pakistan
Institute of Neurogenomics, Helmholtz Zentrum München, Munich, Germany
Institut für Humangenetik, Helmholtz Zentrum München, Munich, Germany
Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University and General Faculty Hospital, Prague, Czech Republic
Human Molecular Genetics Laboratory, Health Biotechnology Division, National Institute for Biotechnology and Genetic Engineering (NIBGE), Faisalabad, Pakistan
Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University and General Faculty Hospital, Prague, Czech Republic
Issue Date: 30-Apr-2019
EDate: 2019-04-30
Citation: Genetics in Medicine 2019; online first: 30 April
Abstract: The purpose of this study was to expand the genetic architecture of neurodevelopmental disorders, and to characterize the clinical features of a novel cohort of affected individuals with variants in ZNF142, a C2H2 domain-containing transcription factor. Four independent research centers used exome sequencing to elucidate the genetic basis of neurodevelopmental phenotypes in four unrelated families. Following bioinformatic filtering, query of control data sets, and secondary variant confirmation, we aggregated findings using an online data sharing platform. We performed in-depth clinical phenotyping in all affected individuals. We identified seven affected females in four pedigrees with likely pathogenic variants in ZNF142 that segregate with recessive disease. Affected cases in three families harbor either nonsense or frameshifting likely pathogenic variants predicted to undergo nonsense mediated decay. One additional trio bears ultrarare missense variants in conserved regions of ZNF142 that are predicted to be damaging to protein function. We performed clinical comparisons across our cohort and noted consistent presence of intellectual disability and speech impairment, with variable manifestation of seizures, tremor, and dystonia. Our aggregate data support a role for ZNF142 in nervous system development and add to the emergent list of zinc finger proteins that contribute to neurocognitive disorders.
URI: http://ahro.austin.org.au/austinjspui/handle/1/20800
DOI: 10.1038/s41436-019-0523-0
ORCID: 0000-0002-8366-4237
0000-0001-8112-9153
0000-0001-7191-8511
0000-0001-5497-8715
0000-0002-9758-9784
0000-0003-0992-4042
0000-0002-2311-2174
0000-0001-5132-0774
0000-0002-4454-8823
0000-0001-8593-3157
0000-0002-2020-9069
0000-0003-3254-5139
0000-0002-0683-5872
0000-0002-2412-8397
0000-0003-2739-0515
0000-0002-2311-2174
PubMed URL: 31036918
Type: Journal Article
Subjects: ataxia
childhood apraxia of speech
developmental delay
dolichocephaly
homozygosity mapping
Appears in Collections:Journal articles

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