Universität zu Köln

Huppke, Peter, Weissbach, Susann, Church, Joseph A., Schnur, Rhonda, Krusen, Martina, Dreha-Kulaczewski, Steffi, Kuehn-Velten, W. Nikolaus, Wolf, Annika, Huppke, Brenda, Millan, Francisca, Begtrup, Amber, Almusafri, Fatima, Thiele, Holger, Altmueller, Janine, Nuernberg, Peter, Mueller, Michael and Gaertner, Jutta (2017). Activating de novo mutations in NFE2L2 encoding NRF2 cause a multisystem disorder. Nat. Commun., 8. LONDON: NATURE PUBLISHING GROUP. ISSN 2041-1723

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Huppke, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Weissbach, Susann UNSPECIFIED UNSPECIFIED UNSPECIFIED Church, Joseph A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schnur, Rhonda UNSPECIFIED UNSPECIFIED UNSPECIFIED Krusen, Martina UNSPECIFIED UNSPECIFIED UNSPECIFIED Dreha-Kulaczewski, Steffi UNSPECIFIED UNSPECIFIED UNSPECIFIED Kuehn-Velten, W. Nikolaus UNSPECIFIED UNSPECIFIED UNSPECIFIED Wolf, Annika UNSPECIFIED UNSPECIFIED UNSPECIFIED Huppke, Brenda UNSPECIFIED UNSPECIFIED UNSPECIFIED Millan, Francisca UNSPECIFIED UNSPECIFIED UNSPECIFIED Begtrup, Amber UNSPECIFIED UNSPECIFIED UNSPECIFIED Almusafri, Fatima UNSPECIFIED UNSPECIFIED UNSPECIFIED Thiele, Holger UNSPECIFIED UNSPECIFIED UNSPECIFIED Altmueller, Janine UNSPECIFIED UNSPECIFIED UNSPECIFIED Nuernberg, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Mueller, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Gaertner, Jutta UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-214374
DOI:	10.1038/s41467-017-00932-7
Journal or Publication Title:	Nat. Commun.
Volume:	8
Date:	2017
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	2041-1723
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SIGNALING PATHWAY; GENE-EXPRESSION; KEAP1; RECOGNITION; MICE; ELECTROPHILES; LANDSCAPE; CARCINOMA; DOMAIN; CELLS Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/21437