DCDC2/内含子2缺失与白质紊乱：聚焦发育性阅读障碍
The DCDC2/intron 2 deletion and white matter disorganization: focus on developmental dyslexia.
作者信息
Marino Cecilia, Scifo Paola, Della Rosa Pasquale A, Mascheretti Sara, Facoetti Andrea, Lorusso Maria L, Giorda Roberto, Consonni Monica, Falini Andrea, Molteni Massimo, Gruen Jeffrey R, Perani Daniela
机构信息
Department of Child Neuropsychiatry, Scientific Institute Eugenio Medea, Bosisio Parini, Italy; Centre de Recherche de l'Institut Universitaire en Santé Mentale de Québec, Québec, Canada; Department of Psychiatry and Neuroscience, Université Laval, Québec, Canada.
C.E.R.M.A.C. (Centro di Risonanza Magnetica ad Alto Campo), Milan, Italy; Department of Nuclear Medicine San Raffaele Hospital and Division of Neuroscience, Scientific Institute San Raffaele, Milan, Italy.
出版信息
Cortex. 2014 Aug;57:227-43. doi: 10.1016/j.cortex.2014.04.016. Epub 2014 May 9.
INTRODUCTION
The DCDC2 gene is involved in neuronal migration. Heterotopias have been found within the white matter of DCDC2-knockdown rats. A deletion in DCDC2/intron 2 (DCDC2d), which encompasses a regulatory region named 'regulatory element associated with dyslexia 1' (READ1), increases the risk for dyslexia. We hypothesized that DCDC2d can be associated to alterations of the white matter structure in general and in dyslexic brains.
METHODS
Based on a full-factorial analysis of covariance (ANCOVA) model, we investigated voxel-based diffusion tensor imaging (VB-DTI) data of four groups of subjects: dyslexia with/without DCDC2d, and normal readers with/without DCDC2d. We also tested DCDC2d effects upon correlation patterns between fractional anisotropy (FA) and reading scores.
RESULTS
We found that FA was reduced in the left arcuate fasciculus and splenium of the corpus callosum in subjects with versus without DCDC2d, irrespective of dyslexia. Subjects with dyslexia and DCDC2d showed reduced FA, mainly in the left hemisphere and in the corpus callosum; their counterpart without DCDC2d showed similar FA alterations. Noteworthy, a conjunction analysis in impaired readers revealed common regions with lower FA mainly in the left hemisphere. When we compared subjects with dyslexia with versus without DCDC2d, we found lower FA in the inferior longitudinal fasciculus and genu of the corpus callosum, bilaterally. Normal readers with versus without DCDC2d had FA increases and decreases in both the right and left hemisphere.
DISCUSSION
The major contribution of our study was to provide evidence relating genes, brain and behaviour. Overall, our findings support the hypothesis that DCDC2d is associated with altered FA. In normal readers, DCDC2-related anatomical patterns may mark some developmental cognitive vulnerability to learning disabilities. In subjects with dyslexia, DCDC2d accounted for both common - mainly located in the left hemisphere - and unique - a more severe and extended pattern - alterations of white matter fibre tracts.
引言
DCDC2基因参与神经元迁移。在DCDC2基因敲低的大鼠白质中发现了异位。DCDC2/内含子2中的一个缺失（DCDC2d），其包含一个名为“与诵读困难相关的调控元件1”（READ1）的调控区域，增加了患诵读困难的风险。我们假设DCDC2d可能与一般白质结构的改变以及诵读困难大脑中的白质结构改变有关。
方法
基于全因素协方差分析（ANCOVA）模型，我们研究了四组受试者基于体素的扩散张量成像（VB-DTI）数据：有/无DCDC2d的诵读困难者，以及有/无DCDC2d的正常阅读者。我们还测试了DCDC2d对分数各向异性（FA）与阅读分数之间相关模式的影响。
结果
我们发现，无论是否患有诵读困难，有DCDC2d的受试者与无DCDC2d的受试者相比，左侧弓状束和胼胝体压部的FA降低。患有诵读困难且有DCDC2d 的受试者FA降低，主要在左半球和胼胝体；没有DCDC2d的对应受试者也表现出类似的FA改变。值得注意的是，对阅读障碍者进行的联合分析显示，FA较低的共同区域主要在左半球。当我们比较有诵读困难且有/无DCDC2d的受试者时，我们发现双侧下纵束和胼胝体膝部的FA较低。有/无DCDC2d的正常阅读者在左右半球的FA均有增加和减少。
讨论
我们研究的主要贡献是提供了基因、大脑和行为之间关系的证据。总体而言，我们的研究结果支持DCDC2d与FA改变有关的假设。在正常阅读者中，与DCDC2相关的解剖模式可能标志着对学习障碍的一些发育性认知易感性。在诵读困难者中，DCDC2d导致了白质纤维束的共同改变（主要位于左半球）和独特改变（更严重且范围更广的模式）。
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