Original Research Article
Altered striatum centered brain structures in SHANK3 deficient Chinese children with genotype and phenotype profiling

https://doi.org/10.1016/j.pneurobio.2020.101985Get rights and content
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open access

Highlights

  • The copy number variation of SHANK3 contributes 0.4 % to Chinese children with ASD.

  • Comprehensive clinical, neurobehavioral, and brain imaging assessments were reported in SHANK3 deficient Chinese children.

  • SHANK3-deficient ASD patients relate to the disrupted striatum centered connectivity.

Abstract

SHANK3 deficiency represents one of the most replicated monogenic risk factors for autism spectrum disorder (ASD) and SHANK3 caused ASD presents a unique opportunity to understand the underlying neuropathological mechanisms of ASD. In this study, genetic tests, comprehensive clinical and neurobehavioral evaluations, as well as multimodal structural MRI using voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) were conducted in SHANK3 group (N = 14 with SHANK3 defects), ASD controls (N = 26 with idiopathic ASD without SHANK3 defects) and typically developing (TD) controls (N = 32). Phenotypically, we reported several new features in Chinese SHANK3 deficient children including anteverted nares, sensory stimulation seeking, dental abnormalities and hematological problems. In SHANK3 group, VBM revealed decreased grey matter volumes mainly in dorsal striatum, amygdala, hippocampus and parahippocampal gyrus; TBSS demonstrated decreased fractional anisotropy in multiple tracts involving projection, association and commissural fibers, including middle cerebral peduncle, corpus callosum, superior longitudinal fasciculus, corona radiata, external and internal capsule, and posterior thalamic radiation, etc. We report that the disrupted striatum centered brain structures are associated with SHANK3 deficient children. Study of subjects with monogenic cause offer specific insights into the neuroimaging studies of ASD. The discovery may support a path for future functional connectivity studies to allow for more in-depth understandings of the abnormal neural circuits and the underlying neuropathological mechanisms for ASD.

Abbreviations

SHANK3
SH3 and multiple ankyrin repeat domains 3
ASD
autism spectrum disorder
TD
typically developing
ADOS-2
autism diagnostic observation schedule-the second edition
DTI
diffusion tensor imaging
VBM
voxel-based morphometry
TBSS
tract-based spatial statistics
FA
fractional anisotropy
MD
mean diffusivity
AAL
automated anatomical labeling
JHU
Johns Hopkins University
DQ
total development quotient
TIV
total intracranial volume
IQR
image quality rating
FD
framewise displacement

Keywords

SHANK3
Autism spectrum disorder
Brain imaging
Voxel-based morphometry
Tract-based spatial statistics
Striatum

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