Deletions in CWH43 cause idiopathic normal pressure hydrocephalus
AuthorsYang, Hong Wei
Carroll, Rona S.
Johnson, Mark D.
Document TypeJournal Article
normal pressure hydrocephalus
Amino Acids, Peptides, and Proteins
Genetics and Genomics
Molecular and Cellular Neuroscience
Nervous System Diseases
MetadataShow full item record
AbstractIdiopathic 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.
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
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/48482
Full author list omitted for brevity. For the full list of authors, see article.