Altered White Matter Organization in the TUBB3 E410K Syndrome.
Cereb Cortex
; 29(8): 3561-3576, 2019 07 22.
Article
em En
| MEDLINE
| ID: mdl-30272120
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.
Palavras-chave
TUBB3; TUBB3 E410K syndrome; arcuate fasciculus (AF); autism; cingulum (Cing); corpus callosum (CC); corticospinal tract (CST); diffusion imaging; dorsal language network (DLN); genetics; inferior fronto-occipital fasciculus (IFOF); inferior longitudinal fasciculus (ILF); intellectual disability, magnetic resonance imaging (MRI); medial lemniscus (ML); misguidance; structural connectivity; superior longitudinal fasciculus (SLF); tractography; uncinate fasciculus (UF); ventral language network (VLN)
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tratos Piramidais
/
Tubulina (Proteína)
/
Córtex Cerebral
/
Corpo Caloso
/
Substância Branca
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Transtorno do Espectro Autista
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Deficiência Intelectual
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Idioma:
En
Revista:
Cereb Cortex
Assunto da revista:
CEREBRO
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos