Strong genetic evidence of DCDC2 as a susceptibility gene for dyslexia.
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.
Schumacher
Johannes
J
Institute of Human Genetics, University of Bonn, Bonn, Germany. johannes.schumacher@uni-bonn.de.
Anthoni
Heidi
H
Dahdouh
Faten
F
König
Inke R
IR
Hillmer
Axel M
AM
Kluck
Nadine
N
Manthey
Malou
M
Plume
Ellen
E
Warnke
Andreas
A
Remschmidt
Helmut
H
Hülsmann
Jutta
J
Cichon
Sven
S
Lindgren
Cecilia M
CM
Propping
Peter
P
Zucchelli
Marco
M
Ziegler
Andreas
A
Peyrard-Janvid
Myriam
M
Schulte-Körne
Gerd
G
Nöthen
Markus M
MM
Kere
Juha
J
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
C510451:DCDC2 protein, human; D017931:DNA Primers; D005819:Genetic Markers; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins