Study of candidate genes for dyslexia in Brazilian individuals

Abstract

ABSTRACT. Dyslexia or reading disability (RD) is the most common childhood learning disorder and a significantly heritable trait. Many recent studies have investigated the genetic basis of dyslexia, and several candidate genes have been proposed. Among these, DCDC2 and KIAA0319 have emerged as the strongest candidate genes for dyslexia; however studies have not provided uniformly supportive results. The aim of this study was to assess the contribution of proposed candidate genes to the molecular etiology of dyslexia in a Brazilian sample. Large deletions and duplications in the candidate genes DCDC2, KIAA0319, and ROBO1 were investigated in 51 dyslexic subjects. Furthermore, a family-based association study was performed to investigate whether associations observed in other populations with variants in the Dyslexia candidate genes DCDC2 and KIAA0319 genes were reproducible in Brazilian dyslexic individuals. Our analysis did not detect any deletions or duplications in the genes studied, and we found no evidence that the allelic variants in the two candidate genes were significantly associated with RD in our sample. Our data do not support a role of the DCDC2/KIAA0319 locus in influencing dyslexia as a categorical trait. Given the genetic complexity of dyslexia, it is plausible that both genes contribute to an increased risk, but the relative influence of these 2 genes on RD varies in different study samples, and/or depends on analytical approaches.

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

“…In KIAA0319, we did not found association of rs9461045, a previously identified causative variant [Dennis et al, 2009] with DD. Our result is consistent with previous association studies from Canadian [Elbert et al, 2011], German [Kirsten et al, 2012], Brazilian [Svidnicki et al, 2013], and Indian populations [Venkatesh et al, 2013] in which rs9461045 failed to associate with DD as well.…”

“…However, association of KIAA0319 with DD was not always consistent. The association of rs9461045 in KIAA0319 with DD failed to be replicated in Canadian [Elbert et al, 2011], German [Kirsten et al, 2012], Brazilian [Svidnicki et al, 2013], and Indian populations [Venkatesh et al, 2013]. In addition, other previously reported genetic variants of KIAA0319 were not shown to associate with DD in some replication studies as well [Brkanac et al, 2007;Ludwig et al, 2008a;Venkatesh et al, 2011;Svidnicki et al, 2013].…”

“…The association of rs9461045 in KIAA0319 with DD failed to be replicated in Canadian [Elbert et al, 2011], German [Kirsten et al, 2012], Brazilian [Svidnicki et al, 2013], and Indian populations [Venkatesh et al, 2013]. In addition, other previously reported genetic variants of KIAA0319 were not shown to associate with DD in some replication studies as well [Brkanac et al, 2007;Ludwig et al, 2008a;Venkatesh et al, 2011;Svidnicki et al, 2013]. The KIAA0319 gene is expressed in human brain [Velayos-Baeza et al, 2007] and encodes a highly N-and O-glycosylated plasma membrane protein with various isoforms due to alternative splicing [Velayos-Baeza et al, 2007;Velayos-Baeza et al, 2008].…”

“…In addition, genetic variants of DCDC2 were also found to be associated with reading abilities in general populations unselected for DD [Lind et al, 2010;Scerri et al, 2011]. However, genetic variants of DCDC2 failed to show any significant association with DD in Indian [Venkatesh et al, 2011;Venkatesh et al, 2013], Brazilian [Svidnicki et al, 2013] and Chinese populations [Zuo et al, 2012]. Nonetheless, genetic polymorphism of DCDC2 seems to be an important risk factor for DD.…”

Caracterização de crianças com dislexia com e sem transtornos de déficit de atenção/hiperatividade

“…Contudo, um estudo realizado para verificar a deleção e duplicação dos genes candidatos DCDC2 e KIAA0319 em uma amostra de disléxicos brasileiros não detectou nenhuma deleção ou duplicação na amostra estudada e concluíram que devido à grande complexidade da genética da dislexia é provável que estes genes contribuam apenas para aumentar o risco para a dislexia e que suas influências variam de acordo com a população estudada (Svidnicki et al, 2013).…”