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. © 2005 by The American Society of Human Genetics. All rights reserved.