Identification of Chiari Type I Malformation subtypes using whole genome expression profiles and cranial base morphometrics.

dc.contributor.author

Markunas, Christina A

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Lock, Eric

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Soldano, Karen

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Cope, Heidi

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Ding, Chien-Kuang C

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Enterline, David S

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Grant, Gerald

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Fuchs, Herbert

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Ashley-Koch, Allison E

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Gregory, Simon G

dc.date.accessioned

2022-09-30T18:12:08Z

dc.date.available

2022-09-30T18:12:08Z

dc.date.issued

2014-06

dc.date.updated

2022-09-30T18:12:07Z

dc.description.abstract

Background

Chiari Type I Malformation (CMI) is characterized by herniation of the cerebellar tonsils through the foramen magnum at the base of the skull, resulting in significant neurologic morbidity. As CMI patients display a high degree of clinical variability and multiple mechanisms have been proposed for tonsillar herniation, it is hypothesized that this heterogeneous disorder is due to multiple genetic and environmental factors. The purpose of the present study was to gain a better understanding of what factors contribute to this heterogeneity by using an unsupervised statistical approach to define disease subtypes within a case-only pediatric population.

Methods

A collection of forty-four pediatric CMI patients were ascertained to identify disease subtypes using whole genome expression profiles generated from patient blood and dura mater tissue samples, and radiological data consisting of posterior fossa (PF) morphometrics. Sparse k-means clustering and an extension to accommodate multiple data sources were used to cluster patients into more homogeneous groups using biological and radiological data both individually and collectively.

Results

All clustering analyses resulted in the significant identification of patient classes, with the pure biological classes derived from patient blood and dura mater samples demonstrating the strongest evidence. Those patient classes were further characterized by identifying enriched biological pathways, as well as correlated cranial base morphological and clinical traits.

Conclusions

Our results implicate several strong biological candidates warranting further investigation from the dura expression analysis and also identified a blood gene expression profile corresponding to a global down-regulation in protein synthesis.
dc.identifier

1755-8794-7-39

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1755-8794

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1755-8794

dc.identifier.uri

https://hdl.handle.net/10161/25905

dc.language

eng

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Springer Science and Business Media LLC

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BMC medical genomics

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10.1186/1755-8794-7-39

dc.subject

Skull

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Humans

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Arnold-Chiari Malformation

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Magnetic Resonance Imaging

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Cluster Analysis

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Gene Expression Profiling

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Gene Expression Regulation

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Genome, Human

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Principal Component Analysis

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Child

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Female

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Male

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Real-Time Polymerase Chain Reaction

dc.title

Identification of Chiari Type I Malformation subtypes using whole genome expression profiles and cranial base morphometrics.

dc.type

Journal article

duke.contributor.orcid

Grant, Gerald|0000-0002-2651-4603

duke.contributor.orcid

Ashley-Koch, Allison E|0000-0001-5409-9155

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Gregory, Simon G|0000-0002-7805-1743

pubs.begin-page

39

pubs.issue

1

pubs.organisational-group

Duke

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Sanford School of Public Policy

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School of Medicine

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Faculty

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Basic Science Departments

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Clinical Science Departments

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Institutes and Centers

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Biostatistics & Bioinformatics

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Molecular Genetics and Microbiology

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Medicine

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Pathology

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Pediatrics

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Radiology

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Medicine, Nephrology

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Radiology, Neuroradiology

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Duke Cancer Institute

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Institutes and Provost's Academic Units

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University Institutes and Centers

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Duke Institute for Brain Sciences

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Duke Molecular Physiology Institute

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Neurosurgery

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Center for Child and Family Policy

pubs.publication-status

Published

pubs.volume

7

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