title: The DCDC2/intron 2 deletion and white matter disorganization: focus on developmental dyslexia.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Marino
authors.affiliation: 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.
authors.forename: Paola
authors.initials: P
authors.lastname: Scifo
authors.affiliation: Institute of Molecular Bioimaging and Physiology, National Research Council, Milan, Italy.
authors.forename: Pasquale A
authors.initials: PA
authors.lastname: Della Rosa
authors.affiliation: Department of Child Neuropsychiatry, Scientific Institute Eugenio Medea, Bosisio Parini, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Mascheretti
authors.affiliation: Department of Child Neuropsychiatry, Scientific Institute Eugenio Medea, Bosisio Parini, Italy; Department of General Psychology and Center for Cognitive Science, University of Padova, Padova, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Facoetti
authors.affiliation: Department of Child Neuropsychiatry, Scientific Institute Eugenio Medea, Bosisio Parini, Italy.
authors.forename: Maria L
authors.initials: ML
authors.lastname: Lorusso
authors.affiliation: Molecular Biology Laboratory, Scientific Institute Eugenio Medea, Bosisio Parini, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Giorda
authors.affiliation: Department of Nuclear Medicine San Raffaele Hospital and Division of Neuroscience, Scientific Institute San Raffaele, Milan, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Consonni
authors.affiliation: C.E.R.M.A.C. (Centro di Risonanza Magnetica ad Alto Campo), Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Falini
authors.affiliation: Department of Child Neuropsychiatry, Scientific Institute Eugenio Medea, Bosisio Parini, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Molteni
authors.affiliation: Department of Pediatrics & Genetics, Yale Child Health Research Center, Yale School of Medicine, New Haven, USA.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Gruen
authors.affiliation: 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; Vita-Salute San Raffaele University, Milan, Italy. Electronic address: daniela.perani@hsr.it.
authors.forename: Daniela
authors.initials: D
authors.lastname: Perani
mesh_terms: D000293:Adolescent; D000328:Adult; D056324:Diffusion Tensor Imaging / Q000379:methods; D004410:Dyslexia / Q000235:genetics*; D005260:Female; D006801:Humans; D007438:Introns / Q000235:genetics*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D009415:Nerve Net / Q000254:growth & development*; D011932:Reading; D066127:White Matter / Q000254:growth & development*; D055815:Young Adult
chemical_list: C510451:DCDC2 protein, human; D008869:Microtubule-Associated Proteins
keywords: DCDC2; Developmental dyslexia; Diffusion tensor imaging; Neuronal migration; READ1