دورية أكاديمية
Deletions in CWH43 cause idiopathic normal pressure hydrocephalus
| العنوان: | Deletions in CWH43 cause idiopathic normal pressure hydrocephalus |
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| المؤلفون: | Hong Wei Yang, Semin Lee, Dejun Yang, Huijun Dai, Yan Zhang, Lei Han, Sijun Zhao, Shuo Zhang, Yan Ma, Marciana F Johnson, Anna K Rattray, Tatyana A Johnson, George Wang, Shaokuan Zheng, Rona S Carroll, Peter J Park, Mark D Johnson |
| المصدر: | EMBO Molecular Medicine, Vol 13, Iss 3, Pp n/a-n/a (2021) |
| بيانات النشر: | Wiley |
| سنة النشر: | 2021 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | CWH43, GPI‐anchored protein, hydrocephalus, normal pressure hydrocephalus, Medicine (General), R5-920, Genetics, QH426-470 |
| الوصف: | Idiopathic normal pressure hydrocephalus (iNPH) is a neurological disorder that occurs in about 1% of individuals over age 60 and is characterized by enlarged cerebral ventricles, gait difficulty, incontinence, and cognitive decline. The cause and pathophysiology of iNPH are largely unknown. We performed whole exome sequencing of DNA obtained from 53 unrelated iNPH patients. Two recurrent heterozygous loss of function deletions in CWH43 were observed in 15% of iNPH patients and were significantly enriched 6.6‐fold and 2.7‐fold, respectively, when compared to the general population. Cwh43 modifies the lipid anchor of glycosylphosphatidylinositol‐anchored proteins. Mice heterozygous for CWH43 deletion appeared grossly normal but displayed hydrocephalus, gait and balance abnormalities, decreased numbers of ependymal cilia, and decreased localization of glycosylphosphatidylinositol‐anchored proteins to the apical surfaces of choroid plexus and ependymal cells. Our findings provide novel mechanistic insights into the origins of iNPH and demonstrate that it represents a distinct disease entity. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1757-4684 1757-4676 |
| العلاقة: | https://doi.org/10.15252/emmm.202013249Test; https://doaj.org/toc/1757-4676Test; https://doaj.org/toc/1757-4684Test; https://doaj.org/article/b927625b6e034f7a94b25a115422a408Test |
| DOI: | 10.15252/emmm.202013249 |
| الإتاحة: | https://doi.org/10.15252/emmm.202013249Test https://doaj.org/article/b927625b6e034f7a94b25a115422a408Test |
| رقم الانضمام: | edsbas.CF46DCA9 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 17574684 17574676 |
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| DOI: | 10.15252/emmm.202013249 |