title: Strong genetic evidence of DCDC2 as a susceptibility gene for dyslexia.
abstract: We searched for linkage disequilibrium (LD) in 137 triads with dyslexia, using markers that span the most-replicated dyslexia susceptibility region on 6p21-p22, and found association between the disease and markers within the VMP/DCDC2/KAAG1 locus. Detailed refinement of the LD region, involving sequencing and genotyping of additional markers, showed significant association within DCDC2 in single-marker and haplotype analyses. The association appeared to be strongest in severely affected patients. In a second step, the study was extended to include an independent sample of 239 triads with dyslexia, in which the association--in particular, with the severe phenotype of dyslexia--was confirmed. Our expression data showed that DCDC2, which contains a doublecortin homology domain that is possibly involved in cortical neuron migration, is expressed in the fetal and adult CNS, which--together with the hypothesized protein function--is in accordance with findings in dyslexic patients with abnormal neuronal migration and maturation.
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn, Germany. johannes.schumacher@uni-bonn.de.
authors.forename: Johannes
authors.initials: J
authors.lastname: Schumacher
authors.forename: Heidi
authors.initials: H
authors.lastname: Anthoni
authors.forename: Faten
authors.initials: F
authors.lastname: Dahdouh
authors.forename: Inke R
authors.initials: IR
authors.lastname: König
authors.forename: Axel M
authors.initials: AM
authors.lastname: Hillmer
authors.forename: Nadine
authors.initials: N
authors.lastname: Kluck
authors.forename: Malou
authors.initials: M
authors.lastname: Manthey
authors.forename: Ellen
authors.initials: E
authors.lastname: Plume
authors.forename: Andreas
authors.initials: A
authors.lastname: Warnke
authors.forename: Helmut
authors.initials: H
authors.lastname: Remschmidt
authors.forename: Jutta
authors.initials: J
authors.lastname: Hülsmann
authors.forename: Sven
authors.initials: S
authors.lastname: Cichon
authors.forename: Cecilia M
authors.initials: CM
authors.lastname: Lindgren
authors.forename: Peter
authors.initials: P
authors.lastname: Propping
authors.forename: Marco
authors.initials: M
authors.lastname: Zucchelli
authors.forename: Andreas
authors.initials: A
authors.lastname: Ziegler
authors.forename: Myriam
authors.initials: M
authors.lastname: Peyrard-Janvid
authors.forename: Gerd
authors.initials: G
authors.lastname: Schulte-Körne
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.forename: Juha
authors.initials: J
authors.lastname: Kere
mesh_terms: D001483:Base Sequence; D015152:Blotting, Northern; D002490:Central Nervous System / Q000378:metabolism; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D017931:DNA Primers; D004410:Dyslexia / Q000235:genetics*; D040461:Gene Components; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005858:Germany; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010641:Phenotype; D017422:Sequence Analysis, DNA
chemical_list: C510451:DCDC2 protein, human; D017931:DNA Primers; D005819:Genetic Markers; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins