دورية أكاديمية
Gain-of-function mutations in KCNK3 cause a developmental disorder with sleep apnea
| العنوان: | Gain-of-function mutations in KCNK3 cause a developmental disorder with sleep apnea |
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| المؤلفون: | Sörmann, J, Schewe, M, Proks, P, Jouen-Tachoire, T, Rao, S, Riel, EB, Agre, KE, Begtrup, A, Dean, J, Descartes, M, Fischer, J, Gardham, A, Lahner, C, Mark, PR, Muppidi, S, Pichurin, PN, Porrmann, J, Schallner, J, Smith, K, Straub, V, Vasudevan, P, Willaert, R, Carpenter, EP, Rödström, KEJ, Hahn, MG, Müller, T, Baukrowitz, T, Hurles, ME, Wright, CF, Tucker, SJ |
| بيانات النشر: | Nature Research |
| سنة النشر: | 2023 |
| المجموعة: | Oxford University Research Archive (ORA) |
| الوصف: | Sleep apnea is a common disorder that represents a global public health burden. KCNK3 encodes TASK-1, a K+ channel implicated in the control of breathing, but its link with sleep apnea remains poorly understood. Here we describe a new developmental disorder with associated sleep apnea (developmental delay with sleep apnea, or DDSA) caused by rare de novo gain-of-function mutations in KCNK3. The mutations cluster around the ‘X-gate’, a gating motif that controls channel opening, and produce overactive channels that no longer respond to inhibition by G-protein-coupled receptor pathways. However, despite their defective X-gating, these mutant channels can still be inhibited by a range of known TASK channel inhibitors. These results not only highlight an important new role for TASK-1 K+ channels and their link with sleep apnea but also identify possible therapeutic strategies. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://ora.ox.ac.uk/objects/uuid:9e4145cc-f7d2-4427-a681-824a5df36a17Test; https://doi.org/10.1038/s41588-022-01185-xTest |
| DOI: | 10.1038/s41588-022-01185-x |
| الإتاحة: | https://doi.org/10.1038/s41588-022-01185-xTest https://ora.ox.ac.uk/objects/uuid:9e4145cc-f7d2-4427-a681-824a5df36a17Test |
| حقوق: | info:eu-repo/semantics/openAccess ; CC Attribution (CC BY) |
| رقم الانضمام: | edsbas.3470E4C7 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41588-022-01185-x |
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