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The DCDC2/intron 2 deletion and white matter disorganization: focus on developmental dyslexia.

ABSTRACT: 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.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.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.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.

SUBMITTER: Marino C

PROVIDER: S-EPMC5975637 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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The DCDC2/intron 2 deletion and white matter disorganization: focus on developmental dyslexia.

Marino Cecilia C Scifo Paola P Della Rosa Pasquale A PA Mascheretti Sara S Facoetti Andrea A Lorusso Maria L ML Giorda Roberto R Consonni Monica M Falini Andrea A Molteni Massimo M Gruen Jeffrey R JR Perani Daniela D

Cortex; a journal devoted to the study of the nervous system and behavior 20140509

<h4>Introduction</h4>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.<h4>Methods</h4>Based on a full-factorial analysis of ...[more]

PMID: 24926531

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Project description:Developmental dyslexia is a complex reading and writing disorder with strong genetic components. In previous genetic studies about dyslexia, a number of candidate genes have been identified. These include DCDC2, which has repeatedly been associated with developmental dyslexia in various European and American populations. However, data regarding this relationship are varied according to population. The Uyghur people of China represent a Eurasian population with an interesting genetic profile. Thus, this group may provide useful information about the association between DCDC2 gene polymorphisms and dyslexia. In the current study, we examined genetic data from 392 Uyghur children aged 8-12 years old from the Xinjiang Uyghur Autonomous Region of China. Participants included 196 children with dyslexia and 196 grade-, age-, and gender-matched controls. DNA was isolated from oral mucosal cell samples and fourteen single nucleotide polymorphisms (rs6456593, rs1419228, rs34647318, rs9467075, rs793862, rs9295619, rs807701, rs807724, rs2274305, rs7765678, rs4599626, rs6922023, rs3765502, and rs1087266) in DCDC2 were screened via the SNPscan method. We compared SNP frequencies in five models (Codominant, Dominant, Recessive, Heterozygote advantage, and Allele) between the two groups by means of the chi-squared test. A single-locus analysis indicated that, with regard to the allele frequency of these polymorphisms, three SNPs (rs807724, rs2274305, and rs4599626) were associated with dyslexia. rs9467075 and rs2274305 displayed significant associations with developmental dyslexia under the dominant model. rs6456593 and rs6922023 were significantly associated with developmental dyslexia under the dominant model and in the heterozygous genotype. Additionally, we discovered that the T-G-C-T of the four-marker haplotype (rs9295619-rs807701-rs807724-rs2274305) and the T-A of the two-marker haplotype (rs3765502-1087266) were significantly different between cases and controls. Thus, we conclude that DCDC2 gene polymorphisms are associated with developmental dyslexia in Chinese Uyghur children.

Dataset Information

The DCDC2/intron 2 deletion and white matter disorganization: focus on developmental dyslexia.

Publications

The DCDC2/intron 2 deletion and white matter disorganization: focus on developmental dyslexia.

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