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| Item Type: | Article |
|---|---|
| Title: | Activating de novo mutations in NFE2L2 encoding NRF2 cause a multisystem disorder |
| Creators Name: | Huppke, P. and Weissbach, S. and Church, J.A. and Schnur, R. and Krusen, M. and Dreha-Kulaczewski, S. and Kühn-Velten, W.N. and Wolf, A. and Huppke, B. and Millan, F. and Begtrup, A. and Almusafri, F. and Thiele, H. and Altmüller, J. and Nürnberg, P. and Müller, M. and Gärtner, J. |
| 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. |
| Keywords: | Binding Sites, Brain, Developmental Disabilities, Failure to Thrive, Gene Expression Regulation, Immunologic Deficiency Syndromes, Kelch-Like ECH-Associated Protein 1, Learning Disabilities, Magnetic Resonance Imaging, Missense Mutation, Mutation, NF-E2-Related Factor 2, Syndrome |
| Source: | Nature Communications |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Volume: | 8 |
| Number: | 1 |
| Page Range: | 818 |
| Date: | 10 October 2017 |
| Official Publication: | https://doi.org/10.1038/s41467-017-00932-7 |
| PubMed: | View item in PubMed |
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