The genetics of reading disability

Abstract

Genetic factors contribute substantially to the development of reading disability (RD). Family linkage studies have implicated many chromosomal regions containing RD susceptibility genes, of which putative loci at 1p34-p36 (DYX8), 2p (DYX3), 6p21.3 (DYX2), and 15q21 (DYX1) have been frequently replicated, whereas those at 3p12-q12 (DYX5), 6q13-q16 (DYX4), 11p15 (DYX7), 18p11 (DYX6), and Xq27 (DYX9) have less evidence. Association studies of positional candidate genes have implicated DCDC2 and KIAA0319 in DYX2, as well as C2ORF3 and MRPL19 (DYX3), whereas DYX1C1/EKN1 (DYX1) and ROBO1 (DYX5) were found to be disrupted by rare translocation breakpoints in reading-disabled individuals. Four of the candidate genes (DYX1C1, KIAA0319, DCDC2, and ROBO1) appear to function in neuronal migration and guidance, suggesting the importance of early neurodevelopmental processes in RD. Future studies to help us understand the function of these and other RD candidate genes promise to yield enormous insight into the neurobiologic mechanisms underlying the pathophysiology of this disorder.

A theoretical molecular network for dyslexia: integrating available genetic findings

“…We found that 10 of the 14 dyslexia candidate genes that were suggested by the literature had been shown to directly or indirectly interact and could be integrated into a molecular signaling network contributing to dyslexia etiology, responsible for regulating neuronal migration and neurite outgrowth. Our work builds on findings of other researchers in the field of dyslexia genetics, 5,[11][12][13] as well as existing knowledge about genes involved in neuronal migration disorders and the KEGG pathway for axon guidance (http:// www.genome.jp/dbget-bin/show_pathway?map043600). Moreover, based on the signaling network, we propose three novel dyslexia candidate genes from linkage regions.…”

“…Considerable effort has been spent in trying to identify the dyslexia genes in a number of these regions by conducting candidate gene association studies, which will be discussed below and in Tables 2 and 3. For additional reviews of the candidate gene association literature of dyslexia, we also refer to Petryshen and Pauls, 5 Scerri and Schulte-Korne 8 and Schumacher et al 40 Until now, no genome-wide association studies (GWAS) for developmental dyslexia have been published. However, Meaburn et al 41 reported a GWAS of early reading (dis)ability in the general population using a quantitative trait loci approach.…”

“…Dyslexia is the most common childhood learning disorder. [1][2][3] The prevalence of dyslexia ranges from 3.6% in primary school children in The Netherlands 4 to as high as 10% in US school-aged children, 5 which is likely due to the fact that many different psychometric tests and diagnostic criteria for dyslexia exist (Box 1). 2,3,6 Twice as many boys as girls are affected with dyslexia.…”

“…The genetic model underlying most cases of dyslexia is likely one in which several to multiple genetic factors, all of small or moderate individual effect size, contribute to disease risk. 3,5 In the current study, we reviewed the available evidence for dyslexia loci and genes, including linkage studies (candidate gene based) association studies and reports of chromosomal aberrations cosegregating with dyslexia. We found that 10 of the 14 dyslexia candidate genes that were suggested by the literature had been shown to directly or indirectly interact and could be integrated into a molecular signaling network contributing to dyslexia etiology, responsible for regulating neuronal migration and neurite outgrowth.…”

SNP Variations in the 7q33 Region Containing DGKI are Associated with Dyslexia in the Finnish and German Populations

“…it is believed that several genes with modest effect sizes contribute to this multi-factorial phenotype affecting 5-10% of school-aged children (Katusic et al 2001;Shaywitz et al 1990). Several candidate genes are described for dyslexia (Smiths 2007;Caylak 2007) and there is evidence for DYX1C1, ROBO1, DCDC2 and KIAA0319 in regulation of neuronal migration, neurite outgrowth and axon pathfinding (Petryshen and Pauls 2009;Poelmans et al 2010). The first candidate gene described for dyslexia, DYX1C1, is the most studied functionally with regards to its role in dyslexia.…”