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disorders, hydrocephalus, renal cysts, and organ inversion left-right asymmetry. Other animal models
have revealed unexpected roles for DYX1C1 in primary cilia which are typical phenotypes of ciliary defects
with similar results in KO mice [138] . Taipale et al. [144] identified a missense mutation (rs57809907, 1249G>T)
in some families with DL. This mutation results in Glu417X with a truncated protein. Later reports found a
correlation with the common G allele. Interestingly, a report of DL in Chinese children also found a strong
[145]
association with the G allele. A allele shows decreased binding to a repressive transcription factor. Lim et al.
hypothesized A allele is protective compared to G allele. Two other SNPs, rs12899331 and rs16787, in the
promoter region were found to be involved in the binding to the transcription factor, but they did not
associate with DL in subsequent studies. Its protein can bind to the estrogenic receptor, suggesting an
involvement of hormonal pathways in dyslexia [146] .

DCDC2
The gene structure is analogous to the DCX gene linked to X, involved in the microtubule structure and
neural migration. Defective DCDC2 causes delays in neural migration in the embryonic brain. The DCX
gene mutation causes lissencephaly in men and cortical abnormalities in women [147] . In vitro studies showed
that sequences in the region act as enhancers of DCDC2 expression. Differences in gene expression may
[82]
have a measurable phenotypic effect on brain structure . Homozygous Dcdc2 KO mice exhibit auditory
processing and memory deficits, as well as electrophysiological changes in cortical neurons with normal
brain development [148] .

Early findings showed that DCDC2 would be a strong candidate for developmental dyslexia. However, some
futher studies did not find its association. Sequence analysis of DCDC2 coding regions in families with DL
has not identified causal mutations; the only correlation of DL was reported with a deletion in intron 2 which
appeared to contain the transcription factor binding sites [149] . This deletion was not found in a further study
on a Hong Kong population [150] . However, it has identified also in a Chinese group of children that the T-G-
C-T of the four-marker haplotypes (rs9295619-rs807701-rs807724-rs2274305) and the T-A of the two-marker
haplotype (rs3765502-1087266) were significantly different between cases and controls [151] .

KIAA0319
Although the role of this gene is unclear, decreased expression in the rat’s embryonic brain leads to delayed
[7]
neural migration . SNPs at 5’UTR, the first untranslated exon and the first intron, suggest regulatory
functions. The first reports linking this gene to dyslexia were described by Francks et al. [152] , identifying
it as a 77-kilobase region of chromosome 6p22.2. Further mapping studies identified KIAA0319 as the
susceptibility gene for dyslexia with risk effects indexed by the rs761100 in intron 1 [153,154] . The expression
of the allele containing the SNP haplotype associated with dyslexia in this region of KIAA0319 decreases
in cell lines of individuals with this pathology. Another SNP, rs9461045, has proven to have a regulatory
function. Reporter trials showed that the risk allele, which was believed to create a binding site for the OCT-
1 repressor, resulted in a decreased expression of KIAA0319. Regions of acetylated histones in and around
the gene were mapped on a neuroblastoma cell line to identify promoting regions. SNPs within or close to
the acetylated region have been correlated with language-disturbing phenotypes, and linkage to the DCDC2/
[85]
KIAA0319 region has been reported for SSD . KIAA0319/TTRAP/THEM2 polymorphisms influence the
laterality of activation in the superior temporal sulcus. Thus, these genes seem to influence the activity of the
two hemispheres asymmetrically in areas related to language function [155] .

Other genes potentially associated with dyslexia
According to animal models, Robo1 gene participates in axonal development across the midline of the
central nervous system and spinal cord [156] . Partial haploinsufficiency may cause dyslexia in humans [157] .

MRPL19 and C2ORF3 are two genes in which their role as co-regulators in dyslexia has been theorized.
The MRPL19 protein is a component of the mitochondrial ribosome, but the function of the C2ORF3 gene