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Genetic Underpinnings of CM and SM and Effect on Brain Development

CM 和 SM 的遗传基础及其对大脑发育的影响

基本信息

批准号：
10629121
负责人：
Gabriel E Haller
金额：
$ 14.46万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-07-01 至 2028-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10629121
关键词：
3-Dimensional Affect Animal Model Bioinformatics Biological Brain Brain Stem Cerebellar tonsil Cerebellum Cerebrospinal Fluid Cerebrospinal fluid shunts procedure Childhood Classification Clinical Clinical Treatment Collaborations Complex Craniosynostosis Cyst Data Data Set Development Disease Disparate Engineering Etiology Fishes Genes Genetic Genetic Models Genetic Variation Genotype Goals Head circumference Human Hydrocephalus Individual Knock-out Lead Liquid substance Macrocephaly Magnetic Resonance Imaging Measurement Methods Microsurgery Modeling Mutation NF1 gene Natural History Neurologic Neurologic Symptoms Neurosurgeon Obstruction Operative Surgical Procedures Outcome Pathology Pathway interactions Patients Phenotype Physiology Positioning Attribute Predictive Factor Proteins Radiology Specialty Risk Role Severities Skeletal system Spinal Canal Spinal Fusion Spine surgery Stents Syringomyelia System Testing Time Tonsil Variant Vertebral column Zebrafish accurate diagnosis body system brain overgrowth brain volume cerebrospinal fluid flow cohort comorbidity cranium de novo mutation exome sequencing foramen magnum gene discovery genetic risk factor genetic variant genome wide association study hindbrain imaging biomarker insight malformation neurosurgery rare variant repaired trait venous sinus ventricular system

项目摘要

PROJECT SUMMARY Chiari type I malformation (CM1), the herniation of the cerebellum through the foramen magnum into the spinal canal, is one of the most common pediatric neurological conditions, found in approximately 1 in 1000 individuals. CM1 is characterized by the herniation of the cerebellum through the foramen magnum into the spinal canal, often leading to syringomyelia (SM), a fluid-filled cyst within the spinal canal, obstruction of normal cerebrospinal fluid flow, compression of the brainstem and numerous neurological symptoms. We now have identified some of the first genetic causes of CM1 and have identified idiopathic macrocephaly as a major etiological subtype of CM1. By identifying additional genetic factors underlying CM1 and CM1-related imaging biomarkers, we hope to uncover additional CM1 subtypes and their genetic basis. Additionally, our goal is to understand the role of CM1- associated genetic variation that we have already identified by modeling specific genetic variants in zebrafish to determine what systems are affected (brain, spine, skull, ventricular system) that lead to the common outcome of hindbrain displacement. Earlier and more accurate diagnoses for CM1 patients will have profound effects, informing clinical decisions regarding who should undergo surgery (versus CSF shunting vs surgery+spinal fusion vs observation, etc) and along what time frame.

项目总结