Marenco Stefano, Siuta Michael A, Kippenhan J Shane, Grodofsky Samuel, Chang Wei-Li, Kohn Philip, Mervis Carolyn B, Morris Colleen A, Weinberger Daniel R, Meyer-Lindenberg Andreas, Pierpaoli Carlo, Berman Karen Faith
Clinical Brain Disorders Branch, Genes Cognition and Psychosis Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.
Proc Natl Acad Sci U S A. 2007 Sep 18;104(38):15117-22. doi: 10.1073/pnas.0704311104. Epub 2007 Sep 7.
Little is known about genetic regulation of the development of white matter. This knowledge is critical in understanding the pathophysiology of neurodevelopmental syndromes associated with altered cognition as well as in elucidating the genetics of normal human cognition. The hemideletion of approximately 25 genes on chromosome 7q11.23 that causes Williams syndrome (WS) includes genes that regulate cytoskeletal dynamics in neurons, especially LIMK1 and CYLN2, and therefore offers the opportunity to investigate the role of these genes in the formation of white matter tracts. We used diffusion tensor imaging to demonstrate alteration in white matter fiber directionality, deviation in posterior fiber tract course, and reduced lateralization of fiber coherence in WS. These abnormalities are consistent with an alteration of the late stages of neuronal migration, define alterations of white matter structures underlying dissociable behavioral phenotypes in WS, and provide human in vivo information about genetic control of white matter tract formation.
关于白质发育的基因调控，我们所知甚少。这一知识对于理解与认知改变相关的神经发育综合征的病理生理学以及阐明正常人类认知的遗传学至关重要。7号染色体长臂11.23区域约25个基因的半缺失导致威廉姆斯综合征（WS），其中包括调控神经元细胞骨架动力学的基因，尤其是LIMK1和CYLN2，因此为研究这些基因在白质束形成中的作用提供了机会。我们使用扩散张量成像来证明WS患者白质纤维方向性改变、后纤维束走行偏差以及纤维相干性的侧向化降低。这些异常与神经元迁移后期的改变一致，确定了WS中可分离行为表型背后的白质结构改变，并提供了关于白质束形成的基因控制的人体体内信息。
