Waye Mary M Y, Poo Lim K, Ho Connie S-H
The Nethersole School of Nursing, The Nethersole School of Nursing, The Chinese University of Hong Kong, Hong Kong.
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong.
Clin Pract Epidemiol Ment Health. 2017 Aug 21;13:104-114. doi: 10.2174/1745017901713010104. eCollection 2017.
Doublecortin domain-containing 2 (DCDC2) is a doublecortin domain-containing gene family member and the doublecortin domain has been demonstrated to bind to tubulin and enhance microtubule polymerization. It has been associated with developmental dyslexia and this protein family member is thought to function in neuronal migration where it may affect the signaling of primary cilia.
The objective of the study is to find out if there is any association of genetic variants of DCDC2 with developmental dyslexia in Chinese children from Hong Kong.
The dyslexic children were diagnosed as developmental dyslexia (DD) using the Hong Kong Test of Specific Learning Difficulties in Reading and Writing (HKT-SpLD) by the Department of Health, Hong Kong. Saliva specimens were collected and their genotypes of DCDC2 were studied by DNA sequencing or TaqMan Real Time PCR Assays.
The most significant marker is rs6940827 which is associated with DD with nominal p-value (0.011). However, this marker did not remain significant after multiple testing corrections and the adjusted p-value from permutation test was 0.1329. Using sliding window haplotype analysis, several haplotypes were found to be nominally associated with DD. The smallest nominal p values was 0.0036 (rs2996452-rs1318700, C-A). However, none of the p values could withstand the multiple testing corrections.
Despite early findings that DCDC2 is a strong candidate for developmental dyslexia and that some of the genetic variants have been linked to brain structure and functions, our findings showed that DCDC2 is not strongly associated with dyslexia.
含双皮质素结构域蛋白2(DCDC2)是含双皮质素结构域基因家族的成员,双皮质素结构域已被证明可与微管蛋白结合并增强微管聚合。它与发育性阅读障碍有关,并且该蛋白家族成员被认为在神经元迁移中发挥作用,在此过程中它可能影响初级纤毛的信号传导。
本研究的目的是查明在中国香港儿童中,DCDC2基因变异与发育性阅读障碍是否存在关联。
阅读障碍儿童通过香港特别行政区卫生署的香港读写特殊学习困难测试(HKT-SpLD)被诊断为发育性阅读障碍(DD)。收集唾液样本,并通过DNA测序或TaqMan实时PCR检测法研究其DCDC2基因的基因型。
最显著的标记是rs6940827,其与DD相关,名义p值为0.011。然而,在进行多重检验校正后,该标记不再显著,置换检验的校正p值为0.1329。使用滑动窗口单倍型分析,发现几种单倍型与DD名义上相关。最小的名义p值为0.0036(rs2996452-rs1318700,C-A)。然而,没有一个p值能够经受多重检验校正。
尽管早期研究结果表明DCDC2是发育性阅读障碍的有力候选基因,并且一些基因变异与脑结构和功能有关,但我们的研究结果表明DCDC2与阅读障碍没有强关联。