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Cited by 15Functional Brain Connectivity StudiesGenetics and Neurodevelopmental DisordersAdvanced Neuroimaging Techniques and Applications

Global and local connectivity differences converge with gene expression in a neurodevelopmental disorder of known genetic origin

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Bathelt, Joe, Barnes, Jessica, Raymond, F Lucy, Baker, Kate, Astle, Duncan·2017·Cerebral Cortex
DOI 10.1093/cercor/bhx027PMC PMC6600876

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Abstract

Knowledge of genetic cause in neurodevelopmental disorders can highlight molecular and cellular processes critical for typical development. Furthermore, the relative homogeneity of neurodevelopmental disorders of known genetic origin allows the researcher to establish the subsequent neurobiological processes that mediate cognitive and behavioral outcomes. The current study investigated white matter structural connectivity in a group of individuals with intellectual disability due to mutations in ZDHHC9. In addition to shared cause of cognitive impairment, these individuals have a shared cognitive profile, involving oromotor control difficulties and expressive language impairment. Analysis of structural network properties using graph theory measures showed global reductions in mean clustering coefficient and efficiency in the ZDHHC9 group, with maximal differences in frontal and parietal areas. Regional variation in clustering coefficient across cortical regions in ZDHHC9 mutation cases was significantly associated with known pattern of expression of ZDHHC9 in the normal adult human brain. The results demonstrate that a mutation in a single gene impacts upon white matter organization across the whole-brain, but also shows regionally specific effects, according to variation in gene expression. Furthermore, these regionally specific patterns may link to specific developmental mechanisms, and correspond to specific cognitive deficits.

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Cited by

Sorted by citations

Authors
Bathelt, J., Barnes, J., Raymond, F. L., Baker, K., & Astle, D.
Affiliations
  • MRC Cognition and Brain Sciences Unit (GB)
  • University of Cambridge (GB)
Corresponding author
Bathelt, Joe
ORCID
Venue
Cerebral Cortex
Publisher
Oxford University Press (OUP)
Published
2017-02-07
Volume
27
Issue
7
Pages
3806-3817
ISSN
  • 1047-3211 (ISSN-L)
  • 1460-2199
DOI
10.1093/cercor/bhx027
PMC
PMC6600876
OpenAlex
W2949313223
Cited by
15
References
7
Citations by year
2025: 1 · 2022: 2 · 2021: 4 · 2020: 2 · 2019: 2 · 2018: 4
FWCI
1.26
Type
journal article
Language
en
Open access
Licence
Locations
  • Cerebral Cortex (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nd)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion, cc-by)
  • Apollo (University of Cambridge) (submittedVersion, cc-by)
  • Apollo (cc-by)
Funders
  • Wellcome Trust (Starter Grant for Clinical Lecturers to K.B)
  • Academy of Medical Sciences (Starter Grant for Clinical Lecturers to K.B)
  • National Institute of Health Research (Academic Clinical Lectureship to K.B., Cambridge Biomedical Research Center to F.L.R.)
  • MRC UK intramural programme (MC-A0606-5PQ41 to J.B. and D.A.)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
Keywords
ZDHHC9, intellectual disability, neurodevelopmental disorders, white matter connectivity, gene expression, graph theory, clustering coefficient, network efficiency, expressive language disorder, frontal and parietal cortex, cognitive impairment
MeSH terms
Acyltransferases, Adolescent, Adult, Mental Disorders, Brain Mapping, Child, Cognition Disorders, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Mutation, Neural Pathways, Gene Expression, Young Adult, Neurodevelopmental Disorders

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