Deletions in CWH43 cause idiopathic normal pressure hydrocephalus
Authors
Yang, Hong WeiYang, Dejun
Dai, Huijun
Zhang, Yan
Zhao, Sijun
Zhang, Shuo
Ma, Yan
Wang, George
Zheng, Shaokuan
Carroll, Rona S.
Johnson, Mark D.
Document Type
Journal ArticlePublication Date
2021-01-18Keywords
CWH43GPI-anchored protein
hydrocephalus
normal pressure hydrocephalus
Amino Acids, Peptides, and Proteins
Genetics and Genomics
Molecular and Cellular Neuroscience
Nervous System Diseases
Neurology
Neurosurgery
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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.Source
Yang HW, Lee S, Yang D, Dai H, Zhang Y, Han L, Zhao S, Zhang S, Ma Y, Johnson MF, Rattray AK, Johnson TA, Wang G, Zheng S, Carroll RS, Park PJ, Johnson MD. Deletions in CWH43 cause idiopathic normal pressure hydrocephalus. EMBO Mol Med. 2021 Jan 18:e13249. doi: 10.15252/emmm.202013249. Epub ahead of print. PMID: 33459505. Link to article on publisher's site
DOI
10.15252/emmm.202013249Permanent Link to this Item
http://hdl.handle.net/20.500.14038/48482PubMed ID
33459505Notes
Full author list omitted for brevity. For the full list of authors, see article.
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Copyright 2021 The Authors. Published under the terms of the CC BY 4.0 license. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.Distribution License
http://creativecommons.org/licenses/by/4.0/ae974a485f413a2113503eed53cd6c53
10.15252/emmm.202013249
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Except where otherwise noted, this item's license is described as Copyright 2021 The Authors. Published under the terms of the CC BY 4.0 license. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.