Nature Communications (Feb 2019)
Biallelic VARS variants cause developmental encephalopathy with microcephaly that is recapitulated in vars knockout zebrafish
- Aleksandra Siekierska,
- Hannah Stamberger,
- Tine Deconinck,
- Stephanie N. Oprescu,
- Michèle Partoens,
- Yifan Zhang,
- Jo Sourbron,
- Elias Adriaenssens,
- Patrick Mullen,
- Patrick Wiencek,
- Katia Hardies,
- Jeong-Soo Lee,
- Hoi-Khoanh Giong,
- Felix Distelmaier,
- Orly Elpeleg,
- Katherine L. Helbig,
- Joseph Hersh,
- Sedat Isikay,
- Elizabeth Jordan,
- Ender Karaca,
- Angela Kecskes,
- James R. Lupski,
- Reka Kovacs-Nagy,
- Patrick May,
- Vinodh Narayanan,
- Manuela Pendziwiat,
- Keri Ramsey,
- Sampathkumar Rangasamy,
- Deepali N. Shinde,
- Ronen Spiegel,
- Vincent Timmerman,
- Sarah von Spiczak,
- Ingo Helbig,
- C4RCD Research Group,
- AR working group of the EuroEPINOMICS RES Consortium,
- Sarah Weckhuysen,
- Christopher Francklyn,
- Anthony Antonellis,
- Peter de Witte,
- Peter De Jonghe
Affiliations
- Aleksandra Siekierska
- Laboratory for Molecular Biodiscovery, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven
- Hannah Stamberger
- Neurogenetics Group, Center for Molecular Neurology, VIB, University of Antwerp
- Tine Deconinck
- Neurogenetics Group, Center for Molecular Neurology, VIB, University of Antwerp
- Stephanie N. Oprescu
- Department of Human Genetics, University of Michigan
- Michèle Partoens
- Laboratory for Molecular Biodiscovery, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven
- Yifan Zhang
- Laboratory for Molecular Biodiscovery, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven
- Jo Sourbron
- Laboratory for Molecular Biodiscovery, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven
- Elias Adriaenssens
- Institute Born Bunge, University of Antwerp
- Patrick Mullen
- Department of Biochemistry, University of Vermont
- Patrick Wiencek
- Department of Biochemistry, University of Vermont
- Katia Hardies
- Neurogenetics Group, Center for Molecular Neurology, VIB, University of Antwerp
- Jeong-Soo Lee
- Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology
- Hoi-Khoanh Giong
- Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology
- Felix Distelmaier
- Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Childrenʼs Hospital, Heinrich-Heine-University Düsseldorf
- Orly Elpeleg
- Monique and Jacques Roboh Department of Genetic Research, Hadassah-Hebrew University Medical Center
- Katherine L. Helbig
- Division of Neurology, Childrenʼs Hospital of Philadelphia
- Joseph Hersh
- Department of Pediatrics, Medicine, University of Louisville School of Medicine
- Sedat Isikay
- Department of Physiotherapy and Rehabilitation, Hasan Kalyoncu University, School of Health Sciences
- Elizabeth Jordan
- The Ohio State University Division of Human Genetics, Department of Internal Medicine
- Ender Karaca
- Department of Molecular and Human Genetics, Baylor College of Medicine
- Angela Kecskes
- Laboratory for Molecular Biodiscovery, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven
- James R. Lupski
- Department of Molecular and Human Genetics, Baylor College of Medicine
- Reka Kovacs-Nagy
- Institute of Human Genetics, Technische Universität München
- Patrick May
- Luxembourg Center for Systems Biomedicine, University Luxembourg
- Vinodh Narayanan
- Center for Rare Childhood Disorders, The Translational Genomics Research Institute
- Manuela Pendziwiat
- Department of Neuropediatrics, Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein
- Keri Ramsey
- Center for Rare Childhood Disorders, The Translational Genomics Research Institute
- Sampathkumar Rangasamy
- Center for Rare Childhood Disorders, The Translational Genomics Research Institute
- Deepali N. Shinde
- Division of Clinical Genomics, Ambry Genetics
- Ronen Spiegel
- Pediatric Department B’ Emek Medical Center
- Vincent Timmerman
- Institute Born Bunge, University of Antwerp
- Sarah von Spiczak
- Department of Neuropediatrics, Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein
- Ingo Helbig
- Division of Neurology, Childrenʼs Hospital of Philadelphia
- C4RCD Research Group
- AR working group of the EuroEPINOMICS RES Consortium
- Sarah Weckhuysen
- Neurogenetics Group, Center for Molecular Neurology, VIB, University of Antwerp
- Christopher Francklyn
- Department of Biochemistry, University of Vermont
- Anthony Antonellis
- Department of Human Genetics, University of Michigan
- Peter de Witte
- Laboratory for Molecular Biodiscovery, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven
- Peter De Jonghe
- Neurogenetics Group, Center for Molecular Neurology, VIB, University of Antwerp
- DOI
- https://doi.org/10.1038/s41467-018-07953-w
- Journal volume & issue
-
Vol. 10,
no. 1
pp. 1 – 15
Abstract
tRNAs are linked with their cognate amino acid by aminoacyl tRNA synthetases (ARS). Here, the authors report a developmental encephalopathy associated with biallelic VARS variants (valyl-tRNA synthetase) that lead to loss of function, as determined by several in vitro assays and a vars knockout zebrafish model.
