Strong genetic evidence of DCDC2 as a susceptibility gene for dyslexia

Am J Hum Genet. 2006 Jan;78(1):52-62. doi: 10.1086/498992. Epub 2005 Nov 17.

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Blotting, Northern
  • Central Nervous System / metabolism
  • Chromosomes, Human, Pair 6 / genetics*
  • DNA Primers
  • Dyslexia / genetics*
  • Gene Components
  • Genetic Markers / genetics
  • Genetic Predisposition to Disease*
  • Genotype
  • Germany
  • Haplotypes / genetics
  • Humans
  • Linkage Disequilibrium
  • Microtubule-Associated Proteins / genetics*
  • Molecular Sequence Data
  • Nerve Tissue Proteins / genetics*
  • Phenotype*
  • Sequence Analysis, DNA

Substances

  • DCDC2 protein, human
  • DNA Primers
  • Genetic Markers
  • Microtubule-Associated Proteins
  • Nerve Tissue Proteins