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Altered White Matter Organization in the TUBB3 E410K Syndrome.

Authors
  • Grant, P Ellen1, 2, 3
  • Im, Kiho2, 3
  • Ahtam, Banu2, 3
  • Laurentys, Cynthia T2, 3
  • Chan, Wai-Man3, 4, 5, 6
  • Brainard, Maya3, 4, 5
  • Chew, Sheena3, 4, 5, 6
  • Drottar, Marie2
  • Robson, Caroline D1, 3
  • Drmic, Irene7
  • Engle, Elizabeth C3, 4, 5, 6, 8
  • 1 Department of Radiology, Boston Children's Hospital, Boston, MA, USA.
  • 2 Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA.
  • 3 Harvard Medical School, Boston, MA, USA.
  • 4 Department of Neurology, Boston Children's Hospital, Boston, MA, USA.
  • 5 F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA, USA.
  • 6 Howard Hughes Medical Institute, Chevy Chase, MD, USA.
  • 7 Hamilton Health Sciences, Ron Joyce Children's Health Centre, Hamilton, Ontario L8L 0A4, Canada. , (Canada)
  • 8 Department of Ophthalmology, Boston Children's Hospital, Boston, MA, USA.
Type
Published Article
Journal
Cerebral Cortex
Publisher
Oxford University Press
Publication Date
Jul 22, 2019
Volume
29
Issue
8
Pages
3561–3576
Identifiers
DOI: 10.1093/cercor/bhy231
PMID: 30272120
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Seven unrelated individuals (four pediatric, three adults) with the TUBB3 E410K syndrome, harboring identical de novo heterozygous TUBB3 c.1228 G>A mutations, underwent neuropsychological testing and neuroimaging. Despite the absence of cortical malformations, they have intellectual and social disabilities. To search for potential etiologies for these deficits, we compared their brain's structural and white matter organization to 22 controls using structural and diffusion magnetic resonance imaging. Diffusion images were processed to calculate fractional anisotropy (FA) and perform tract reconstructions. Cortical parcellation-based network analysis and gyral topology-based FA analyses were performed. Major interhemispheric, projection and intrahemispheric tracts were manually segmented. Subjects had decreased corpus callosum volume and decreased network efficiency. While only pediatric subjects had diffuse decreases in FA predominantly affecting mid- and long-range tracts, only adult subjects had white matter volume loss associated with decreased cortical surface area. All subjects showed aberrant corticospinal tract trajectory and bilateral absence of the dorsal language network long segment. Furthermore, pediatric subjects had more tracts with decreased FA compared with controls than did adult subjects. These findings define a TUBB3 E410K neuroimaging endophenotype and lead to the hypothesis that the age-related changes are due to microscopic intrahemispheric misguided axons that are pruned during maturation. © The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: [email protected]

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