Putative miRNAs for the diagnosis of dyslexia, dyspraxia, and specific language impairment

Figures & data

Table 1. Common miRNAs (RefSeq ID) of dyslexia, dyspraxia, and SLI genes

Target genes	Common miRNAs	Context score
Dyslexia: C2orf3 DCDC2 DYX1C1 KIAA0319 KIAA0319L MRPL19 ROBO1	hsa-miR-548c-3p	> - 0.01 - 0.05 > - 0.01 > - 0.01 > - 0.01 - 0.04 - 0.19
Dyspraxia: NAGPA FOXP2	hsa-miR-182 hsa-miR-34c-5p hsa-miR-34a hsa-miR-449a hsa-miR-449b hsa-miR-1271 hsa-miR-96 hsa-miR-9 hsa-miR-647 hsa-miR-604 hsa-miR-214 hsa-miR-657	- 0.22 - 0.17 - 0.17 - 0.17 - 0.17 > - 0.02 - 0.04 > - 0.01 - 0.12 - 0.06 - 0.15 - 0.09
SLI: CNTNAP2 ATP2C2 CMIP	hsa-miR-1207–5p hsa-miR-188–3p hsa-miR-1225–3p hsa-miR-299–3p	- 0.02 - 0.10 - 0.09 > - 0.01
Dyslexia + Dyspraxia (8/9 genes)	hsa-miR-548c-3p
Dyslexia + SLI (9/10 genes)	hsa-miR-548c-3p
SLI + Dyspraxia (4/5 genes)	hsa-miR-1207–5p
Dyslexia + SLI + Dyspraxia (10/12 genes)	hsa-miR-548c-3p

We report target genes (first column), common miRNAs (second column), and context score (third column). More negative context scores indicate sites predicted to be in more favorable contexts for miRNA recognition.¹⁸ The analysis was performed combining genes implicated in dyslexia, dyspraxia, and SLI and showed common miRNAs to almost all the genes. The database used for this analysis was TargetScan.

Table 2. Axon guidance pathway modulated by the identified miRNAs

Axon guidance target genes	Common miRNAs
Dyslexia: EPHA3, NTNG1, ABLIM3, PLXNA1, EPHB2, MET, SRGAP2, SLIT3, SEMA4C, UNC5D, MAPK1, EFNA4, PAK2, PPP3CA, NFAT5, SLIT2	hsa-miR-548c-3p
Dyspraxia: EFNB2, ABLIM1, GNAI3, ROCK1, L1CAM, EFNA5, EPHA7, CFL1, RAC1, PPP3CA, RASA1, SEMA5A GNAI2, ABLIM1, MET, SEMA4C, SEMA4F EFNB2, ABLIM1, GNAI3, ROCK1, L1CAM, EFNA5 EFNB2, ABLIM1, GNAI3, ROCK1, L1CAM, EFNA5 SRGAP3, PLXNA2, NTNG1, EPHB2, SEMA6D, EPHA7, NRP1, PAK4, PAK2, PAK6, DCC, EPHB4, EFNA1 DPYSL2, SEMA4D, PAK6 DPYSL2 SRGAP3, SEMA6A, GNAI2, LIMK2, SEMA3D, SEMA5A, NTN1 SRGAP3, DPYSL2, MET	hsa-miR-182 hsa-miR-34a hsa-miR-1271 hsa-miR-96 hsa-miR-9 hsa-miR-647 hsa-miR-604 hsa-miR-214 hsa-miR-657
SLI: SRGAP3, GNAI2, ABLIM3, CFL1, UNC5A, EFNB1 SRGAP3, PLXNA1 NCK2, EPHA7	hsa-miR-1207–5p hsa-miR-188–3p hsa-miR-299–3p
Dyslexia + Dyspraxia: EPHA3, NTNG1, ABLIM3, PLXNA1, EPHB2, MET, SRGAP2, SLIT3, SEMA4C, UNC5D, MAPK1, EFNA4, PAK2, PPP3CA, NFAT5, SLIT2	hsa-miR-548c-3p
Dyslexia + SLI: EPHA3, NTNG1, ABLIM3, PLXNA1, EPHB2, MET, SRGAP2, SLIT3, SEMA4C, UNC5D, MAPK1, EFNA4, PAK2, PPP3CA, NFAT5, SLIT2	hsa-miR-548c-3p
Group 3: SLI + Dyspraxia: SRGAP3, GNAI2, ABLIM3, CFL1, UNC5A, EFNB1	hsa-miR-1207–5p
Dyslexia + SLI + Dyspraxia: EPHA3, NTNG1, ABLIM3, PLXNA1, EPHB2, MET, SRGAP2, SLIT3, SEMA4C, UNC5D, MAPK1, EFNA4, PAK2, PPP3CA, NFAT5, SLIT2	hsa-miR-548c-3p

We report target genes of the axon guidance pathway (in the first column) modulated by the common miRNAs (second column). We indicate only the axon guidance target genes of the involved miRNAs. The database used for this analysis was TargetScan.

Figure 1. Targets of the axon guidance pathway, possibly modulated by miRNAs in dyslexia (green bar), dyspraxia (red bar), and SLI (blue bar). The interactions are based on hsa04360 KEGG pathway description (http://www.genome.jp/dbget-bin/www_bget?pathway+hsa04360) and literature (see section 5).

Figure 2. Targets of the axon guidance pathway likely altered in dyspraxia. The comparison of Figure 2 with Figure 1 denotes the possible importance of semaphorin signaling in the pathology of dyspraxia, while ephrin and netrin signaling are present too. As can be seen, the pathways lead to a favoring of axon repulsion through the PAK kinases and to axon attraction through RAC1; therefore, possible loss of balance between axon repulsion and axon attraction could be the result of deregulated expression of the semaphorin signaling.

Garcia DM, Baek D, Shin C, Bell GW, Grimson A, Bartel DP. Weak seed-pairing stability and high target-site abundance decrease the proficiency of lsy-6 and other microRNAs. Nat Struct Mol Biol 2011; 18:1139 - 46; http://dx.doi.org/10.1038/nsmb.2115; PMID: 21909094

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