Owen Julia P, Chang Yi Shin, Pojman Nicholas J, Bukshpun Polina, Wakahiro Mari L J, Marco Elysa J, Berman Jeffrey I, Spiro John E, Chung Wendy K, Buckner Randy L, Roberts Timothy P L, Nagarajan Srikantan S, Sherr Elliott H, Mukherjee Pratik
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.
J Neurosci. 2014 Apr 30;34(18):6214-23. doi: 10.1523/JNEUROSCI.4495-13.2014.
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.
染色体位点16p11.2的拷贝数变异（CNV），包括缺失或重复，与自闭症、精神分裂症、癫痫和其他神经精神疾病有关。由于在这些更广泛定义的临床疾病中可以观察到白质微观结构异常，我们使用扩散磁共振成像和基于束的空间统计学方法，来研究患有16p11.2缺失的儿童的白质微观结构完整性。我们发现，与发育正常的匹配对照组相比，缺失携带者在许多主要的中央白质束中，包括胼胝体前部以及双侧内囊和外囊，轴向扩散率（AD）增加。在缺失携带者中，较高的AD与较低的非语言智商相关，但在对照组中则不然。在一些AD升高的相同白质束中，也发现了各向异性分数和平均扩散率的增加。通过神经突方向离散度和密度成像进行更仔细的检查发现，一些中央白质束中的纤维方向离散度降低。值得注意的是，这些白质改变不同于其他任何神经发育障碍所报道的微观结构差异，包括与缺失携带者有表型重叠的自闭症谱系障碍。这些发现表明，16p11.2位点的缺失与一种独特的广泛存在的白质微观结构异常模式有关，这种模式可能是该CNV认知受损特征的基础。
