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J Neurosci. 2014 Apr 30;34(18):6214-23. doi: 10.1523/JNEUROSCI.4495-13.2014.

Aberrant white matter microstructure in children with 16p11.2 deletions.

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Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California 94107, Program in Bioengineering, Department of Neurology, University of California, San Francisco, San Francisco, California 94158, Department of Radiology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, Simons Foundation, New York, New York 10010, Departments of Pediatrics and Medicine, Columbia University Medical Center, New York, New York 10032, and Center for Brain Science, Harvard University, Cambridge, Massachusetts 02138.


Copy number variants (CNVs) of the chromosomal locus 16p11.2, consisting of either deletions or duplications, have been implicated in autism, schizophrenia, epilepsy, and other neuropsychiatric disorders. Since abnormal white matter microstructure can be seen in these more broadly defined clinical disorders, we used diffusion magnetic resonance imaging and tract-based spatial statistics to investigate white matter microstructural integrity in human children with 16p11.2 deletions. We show that deletion carriers, compared with typically developing matched controls, have increased axial diffusivity (AD) in many major central white matter tracts, including the anterior corpus callosum as well as bilateral internal and external capsules. Higher AD correlated with lower nonverbal IQ in the deletion carriers, but not controls. Increases in fractional anisotropy and mean diffusivity were also found in some of the same tracts with elevated AD. Closer examination with neurite orientation dispersion and density imaging revealed that fiber orientation dispersion was decreased in some central white matter tracts. Notably, these alterations of white matter are unlike microstructural differences reported for any other neurodevelopmental disorders, including autism spectrum disorders that have phenotypic overlap with the deletion carriers. These findings suggest that deletion of the 16p11.2 locus is associated with a unique widespread pattern of aberrant white matter microstructure that may underlie the impaired cognition characteristic of this CNV.


autism; copy number variants; diffusion tensor imaging; genetics; magnetic resonance imaging; neurodevelopmental disorders

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