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
Institute of Human Genetics, University of Bonn, Bonn, Germany.
Am J Hum Genet. 2006 Jan;78(1):52-62. doi: 10.1086/498992. Epub 2005 Nov 17.
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.
我们利用跨越6号染色体短臂21区至22区最常被复制的诵读困难易感区域的标记，在137个患有诵读困难的三联体中寻找连锁不平衡（LD），并发现该疾病与VMP/DCDC2/KAAG1基因座内的标记之间存在关联。对LD区域进行的详细细化，包括对额外标记进行测序和基因分型，在单标记和单倍型分析中显示DCDC2内存在显著关联。这种关联在受影响严重的患者中似乎最为强烈。第二步，该研究扩展至纳入239个患有诵读困难的三联体的独立样本，其中这种关联——尤其是与诵读困难的严重表型的关联——得到了证实。我们的表达数据表明，DCDC2含有一个可能参与皮层神经元迁移的双皮质素同源结构域，在胎儿和成人的中枢神经系统中均有表达，这与推测的蛋白质功能一起，与神经元迁移和成熟异常的诵读困难患者的研究结果一致。
