Strong Genetic Evidence of DCDC2 as a Susceptibility Gene for Dyslexia

• Published in: American journal of human genetics Vol. 78; no. 1; pp. 52 - 62
• Main Authors: Schumacher, Johannes, Anthoni, Heidi, Dahdouh, Faten, König, Inke R., Hillmer, Axel M., Kluck, Nadine, Manthey, Malou, Plume, Ellen, Warnke, Andreas, Remschmidt, Helmut, Hülsmann, Jutta, Cichon, Sven, Lindgren, Cecilia M., Propping, Peter, Zucchelli, Marco, Ziegler, Andreas, Peyrard-Janvid, Myriam, Schulte-Körne, Gerd, Nöthen, Markus M., Kere, Juha
• Format: Journal Article
• Language: English
• Published: Chicago, IL Elsevier Inc 01.01.2006; University of Chicago Press; Cell Press; The American Society of Human Genetics
• Subjects: Base Sequence; Biological and medical sciences; Blotting, Northern; Central Nervous System - metabolism; Children & youth; Chromosomes, Human, Pair 6 - genetics; Disorders of higher nervous function. Focal brain diseases. Central vestibular syndrome and deafness. Brain stem syndromes; DNA Primers; Dyslexia; Dyslexia - genetics; Gene Components; General aspects. Genetic counseling; Genes; Genetic Markers - genetics; Genetic Predisposition to Disease; Genetics; Genotype; Germany; Haplotypes - genetics; Humans; Learning; Linkage Disequilibrium; Medical genetics; Medical sciences; Medicin och hälsovetenskap; Microtubule-Associated Proteins - genetics; Molecular Sequence Data; Nerve Tissue Proteins - genetics; Nervous system (semeiology, syndromes); Neurology; Parents & parenting; Phenotype; Sequence Analysis, DNA; Studies; Germany; Human; Communication disorder; Nervous system diseases; Sensitivity; Reading disorder; Predisposition; Dyslexia; Genetics; Neurological disorder; Genetic determinism; Language disorder
• ISSN: 0002-9297; 1537-6605
• DOI: 10.1086/498992

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.