Investigation of the DCDC2 intron 2 deletion/compound short tandem repeat polymorphism in a large German dyslexia sample

Abstract

Dyslexia is a complex disorder manifested by difficulties in learning to read and spell despite conventional instruction, adequate intelligence and sociocultural opportunity. It is among the most common neurodevelopmental disorders with a prevalence of 5-12%. The dyslexia susceptibility locus 2 on chromosome 6p21-p22 is one of the best-replicated linkage regions in dyslexia. On the basis of systematic linkage disequilibrium studies, the doublecortin domain containing protein 2 gene (DCDC2) was identified as a strong candidate gene in this region. Data from a US study have suggested a complex deletion/compound short tandem repeat (STR) polymorphism in intron 2 of DCDC2 as the causative mutation. In this study, we analyzed this polymorphism in 396 German dyslexia trios which included 376 trios previously providing strong support for the DCDC2 locus. We observed no significant deviation from random transmission, neither for the deletion nor for the alleles of the compound STR. We also did not find the deletion or any of the STR alleles to be in linkage disequilibrium with the 2-marker haplotype, which was associated with dyslexia in our sample. We thus conclude that the causative variant/s in DCDC2 conferring susceptibility to dyslexia in our sample remain/s to be identified.

Genetics of developmental dyslexia

“…Association with DCDC2 was also first observed in samples from the CLDRC [40]. In all, five of the six independent DD studies that have been tested recently, association has been found between DCDC2 and a variety of markers across the 212 kb length of this gene [18,31,40,59,80,95,112,121,158]. Several noteworthy genetic variants have been identified in DCDC2 which have produced mixed results when tested in independent samples.…”

“…Several noteworthy genetic variants have been identified in DCDC2 which have produced mixed results when tested in independent samples. A polymorphic deletion has been associated in three of six studies [18,80,112,121], and the SNP rs793862 in four of the six independent DD studies [18,40,80,121,158]. A haplotype of rs793862 and another SNP, rs807701, has also proved significant association in two of five DD studies [158].…”

A theoretical molecular network for dyslexia: integrating available genetic findings

“…30,64 Of these five genes, genetic variants in DCDC2, KIAA0319 and TTRAP were reported to be associated with the disorder more than once 3,52,[65][66][67][68][69][70][71][72][73][74][75][76][77] ( Table 3).…”

Dyslexia and DCDC2: normal variation in reading and spelling is associated with DCDC2 polymorphisms in an Australian population sample

“…Although this deletion in conjunction with the STR was significantly associated with reading performance in US families, 9 the association was either weak or absent in United Kingdom and German cohorts. 7,15 However, a recent voxel-based morphometry study 16 showed a positive correlation between the deletion and variation in gray matter volume in brain regions previously associated with language.…”