期刊
NATURE MEDICINE
卷 26, 期 11, 页码 1754-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41591-020-1090-2
关键词
-
资金
- Hydrocephalus Association (HA)
- Yale-National Institutes of Health (NIH) Center for Mendelian Genomics [5U54HG006504]
- NIH Director's Pioneer Award [DP1HD086071]
- NIH Director's Transformative Award [1R01AI145057]
- NIH Medical Scientist Training Program (NIH/National Institute of General Medical Sciences) [T32GM007205]
- NIH Clinical and Translational Science Award from the National Center for Advancing Translational Science [TL1 TR001864]
- James Hudson Brown - Alexander B. Coxe Fellowship at Yale School of Medicine
- American Heart Association Postdoctoral Fellowship [18POST34060008]
- K99/R00 Pathway to Independence Award [K99HL143036, R00HL143036-02]
- American Heart Association Predoctoral Fellowship [19PRE34380842]
- Pediatric Hydrocephalus Foundation
- Rudi Schulte Research Institute
- [R01 NS111029-01A1]
- [R01 NS109358]
- [K12 228168]
Congenital hydrocephalus (CH), characterized by enlarged brain ventricles, is considered a disease of excessive cerebrospinal fluid (CSF) accumulation and thereby treated with neurosurgical CSF diversion with high morbidity and failure rates. The poor neurodevelopmental outcomes and persistence of ventriculomegaly in some post-surgical patients highlight our limited knowledge of disease mechanisms. Through whole-exome sequencing of 381 patients (232 trios) with sporadic, neurosurgically treated CH, we found that damaging de novo mutations account for >17% of cases, with five different genes exhibiting a significant de novo mutation burden. In all, rare, damaging mutations with large effect contributed to similar to 22% of sporadic CH cases. Multiple CH genes are key regulators of neural stem cell biology and converge in human transcriptional networks and cell types pertinent for fetal neuro-gliogenesis. These data implicate genetic disruption of early brain development, not impaired CSF dynamics, as the primary pathomechanism of a significant number of patients with sporadic CH.
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