Activating de novo mutations in NFE2L2 encoding NRF2 cause a multisystem disorder

Peter Huppke (), Susann Weissbach, Joseph A. Church, Rhonda Schnur, Martina Krusen, Steffi Dreha-Kulaczewski, W. Nikolaus Kühn-Velten, Annika Wolf, Brenda Huppke, Francisca Millan, Amber Begtrup, Fatima Almusafri, Holger Thiele, Janine Altmüller, Peter Nürnberg, Michael Müller and Jutta Gärtner
Additional contact information
Peter Huppke: Division of Pediatric Neurology, University Medical Center Göttingen
Susann Weissbach: Division of Pediatric Neurology, University Medical Center Göttingen
Joseph A. Church: Divison of Clinical Immunology and Allergy, Childrens Hospital Los Angeles, and Keck School of Medicine University of Southern California
Rhonda Schnur: Division of Genetics, Cooper University Health Care, Cooper Medical School of Rowan University 3
Martina Krusen: Lebenszentrum Königsborn Fachklinik für Kinderneurologie und Sozialpädiatrie mit Sozialpädiatrischem Zentrum
Steffi Dreha-Kulaczewski: Division of Pediatric Neurology, University Medical Center Göttingen
W. Nikolaus Kühn-Velten: Medical Laboratory Bremen
Annika Wolf: Division of Pediatric Neurology, University Medical Center Göttingen
Brenda Huppke: Division of Pediatric Neurology, University Medical Center Göttingen
Francisca Millan: GeneDx
Amber Begtrup: GeneDx
Fatima Almusafri: Clinical and Metabolic Genetics, Hamad Medical Corporation
Holger Thiele: Cologne Center for Genomics (CCG), University of Cologne
Janine Altmüller: Cologne Center for Genomics (CCG), University of Cologne
Peter Nürnberg: Cologne Center for Genomics (CCG), University of Cologne
Michael Müller: Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB)
Jutta Gärtner: Division of Pediatric Neurology, University Medical Center Göttingen

Nature Communications, 2017, vol. 8, issue 1, 1-10

Abstract: Abstract Transcription factor NRF2, encoded by NFE2L2, is the master regulator of defense against stress in mammalian cells. Somatic mutations of NFE2L2 leading to NRF2 accumulation promote cell survival and drug resistance in cancer cells. Here we show that the same mutations as inborn de novo mutations cause an early onset multisystem disorder with failure to thrive, immunodeficiency and neurological symptoms. NRF2 accumulation leads to widespread misregulation of gene expression and an imbalance in cytosolic redox balance. The unique combination of white matter lesions, hypohomocysteinaemia and increased G-6-P-dehydrogenase activity will facilitate early diagnosis and therapeutic intervention of this novel disorder.

Date: 2017
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-017-00932-7 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00932-7

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-017-00932-7

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().