期刊
EMBO MOLECULAR MEDICINE
卷 13, 期 3, 页码 -出版社
WILEY
DOI: 10.15252/emmm.202013249
关键词
CWH43; GPI-anchored protein; hydrocephalus; normal pressure hydrocephalus
资金
- NIH from the National Institute of Neurological Disorders and Stroke [R01 NS106985, R56 NS100511]
Idiopathic normal pressure hydrocephalus (iNPH) is a rare neurological disorder characterized by enlarged cerebral ventricles, gait difficulty, and cognitive decline. A study found that heterozygous loss of function deletions in the CWH43 gene may be associated with the disease, providing new insights into its origins.
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据