DCDC2 genetic variants and susceptibility to developmental dyslexia

Abstract

Objective(s) Developmental Dyslexia is a heritable condition, with genetic factors accounting for 44%–75% of the variance in performance tests of reading component subphenotypes. Compelling genetic linkage and association evidence supports a quantitative trait locus in the 6p21.3 region, which encodes a gene called DCDC2. In the present study, we explored the contribution of two DCDC2 markers to dyslexia, related reading and memory phenotypes in nuclear families of Italian origin. Methods 303 nuclear families recruited on the basis of having a proband with Developmental Dyslexia have been studied with 6p21.3 markers, BV677278 and rs793862. Marker-trait association was investigated by the quantitative transmission disequilibrium test (QTDT, version 2.5.1) as modelled by Abecasis et al. (2000), which allows for the analyses of quantitative traits. Seven phenotypes were used in association analyses, i.e. word and non-word reading, word and non-word spelling, orthographic choice, memory and the affected status based on inclusion criteria. Results QTDT analyses yielded evidence for association between reading skills and the BV677278 deletion (empirical p-values= .025–.029) and between memory and BV677278 allele 10 (empirical p-value= .0001). Conclusions Our result adds further evidence in support of DCDC2 contributing to the deficits in Developmental Dyslexia. More specifically, our data support the view that DCDC2 influences both reading and memory impairments thus shedding further light into the etiologic basis and the phenotypic complexity of Developmental Dyslexia.

Association study of developmental dyslexia candidate genes DCDC2 and KIAA0319 in Chinese population

“…Additionally, rs793862 and rs807724 failed to show any significant association with DD in our cohort as well. This is consistent with a previous study of German population in which no association was found between rs793862 and DD [Marino et al, 2012]. In KIAA0319, we did not found association of rs9461045, a previously identified causative variant [Dennis et al, 2009] with DD.…”

“…Previously identified functional variants have been replicated, including BV677278 of DCDC2 [Brkanac et al, 2007;Ludwig et al, 2008b;Wilcke et al, 2009;Meng et al, 2011;Marino et al, 2012;Powers et al, 2013] and rs9461045 of KIAA0319 [Elbert et al, 2011;Kirsten et al, 2012;Svidnicki et al, 2013;Venkatesh et al, 2013]. The results were inconclusive across different populations.…”

Neural Noise Hypothesis of Developmental Dyslexia

“…An increasing number of studies have investigated the function of RD risk genes in animal models [2][3][4][5][6][7][8][9][10][11][12][13], and the neurobiological and behavioral consequences of genetic RD risk variants in humans [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31], motivating the need for a synthesis of these findings, especially because they relate to emerging avenues of human research on the role of neurochemistry [32] and neural oscillations [33][34][35][36] in RD. Here, we present a timely integration of diverse lines of current research linking some of the key neural and behavioral deficits associated with RD to basic neural processes.…”

Relying on brain rhythms for improving the diagnosis of dyslexia

“…Since an early diagnosis of developmental cognitive disorders usually results in better outcomes at later ages, particularly because it allows intervention aimed to prevent rather than remediate reading difficulties, there is a great interest for 4 identifying early markers of dyslexia. Predictors of developmental dyslexia in preliterate children include i) behavioural and language measures, such as language delay, problems with naming, difficulties for recognizing and manipulating rhymes, and/or attention/comprehension problems (Flax, Realpe-Bonilla, Roesler, Choudhury, & Benasich, 2009;Puolakanaho et al, 2008;Vanvooren, Poelmans, De Vos, Ghesquière, & Wouters, 2017); ii) neurobiological signatures, such as changes in brain connectivity, alterations of grey matter volumes, or abnormal patters of brain activity (Noordenbos, Segers, Wagensveld, & Verhoeven, 2013;Raschle, Chang, & Gaab, 2011;Skeide et al, 2015;van Zuijen, Plakas, Maassen, Maurits, & van der Leij, 2013); and iii) genetic data, like mutations in candidate genes for the condition, many of which typically contribute to the development and wiring of brain areas involved in reading (Marino et al, 2012;Paracchini et al, 2011, Paracchini, Diaz, & Stein, 2016. Nonetheless, neither of these measures and signatures is expected to be specific to dyslexia and they might well fail to predict the onset of the disease (see Lyytinen, Erskine, Hämäläinen, Torppa, & Ronimus, 2015;Ozernov-Palchik & Gaab, 2016;Thompson et al, 2015 for a discussion).…”