The roles of genes in the neuronal migration and neurite outgrowth network in developmental dyslexia: single- and multiple-risk genetic variants.
Abstract
Abnormal regulation of neural migration and neurite growth is thought to be an important feature of developmental dyslexia (DD). We investigated 16 genetic variants, selected by bioinformatics analyses, in six key genes in the neuronal migration and neurite outgrowth network in a Chinese population. We first observed that KIAA0319L rs28366021, KIAA0319 rs4504469, and DOCK4 rs2074130 were significantly associated with DD risk after false discovery rate (FDR) adjustment for multiple comparisons (odds ratio (OR) = 0.672, 95 % confidence interval (CI) = 0.505-0.894, P = 0.006; OR = 1.608, 95 % CI = 1.174-2.203, P = 0.003; OR = 1.681, 95 % CI = 1.203-2.348, P = 0.002). The following classification and regression tree (CART) analysis revealed a prediction value of gene-gene interactions among DOCK4 rs2074130, KIAA0319 rs4504469, DCDC2 rs2274305, and KIAA0319L rs28366021 variants. Compared with the lowest risk carriers of the combination of rs2074130 CC, rs4504469 CC, and rs2274305 GG genotype, individuals carrying the combined genotypes of rs2074130 CC, rs4504469 CT or TT, and rs28366021 GG had a significantly increased risk for DD (OR = 2.492, 95 % CI = 1.447-4.290, P = 0.001); individuals with the combination of rs2074130 CT or TT and rs28366021 GG genotype exhibited the highest risk for DD (OR = 2.770, 95 % CI = 2.265-6.276, P = 0.000). A significant dose effect was observed among these four variants (P for trend = 0.000). In summary, this study supports the importance of single…
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Two specific DOCK4 variations, Exon27-52 deletion (Dock4-945VS) and rs2074130 missense (Dock4-R853H), are associated with dyslexia and/or ASD with reading difficulties.
“Two DOCK4 variations, Exon27-52 deletion (protein product: Dock4-945VS) and a missense mutation at rs2074130 (protein product: Dock4-R853H), are associated with dyslexia and/or ASD with reading difficulties.”
From Two Autism/Dyslexia Linked Variations of DOCK4 Disrupt the Gene Function on Rac1/Rap1 Activation, Neurite Outgrowth, and Synapse Development (2020) · cites this paper as Shao et al., 2016
DOCK4 is one of few genes associated with both autism spectrum disorder (ASD) and dyslexia.
“DOCK4 (dedicator for cytokinesis 4), a guanine nucleotide exchange factor (GEF) for the small GTPase Rac1, is one of few genes that are associated with both ASD and dyslexia.”
From Two Autism/Dyslexia Linked Variations of DOCK4 Disrupt the Gene Function on Rac1/Rap1 Activation, Neurite Outgrowth, and Synapse Development (2020) · cites this paper as Shao et al., 2016
The rs20741307 variation causes a missense mutation substituting Arginine at residue 853 with Histidine (Dock4-R853H).
“p.R853H”
From Two Autism/Dyslexia Linked Variations of DOCK4 Disrupt the Gene Function on Rac1/Rap1 Activation, Neurite Outgrowth, and Synapse Development (2020) · cites this paper as Shao et al., 2016
Disruptions of neuronal migration and neurite outgrowth contribute importantly to the pathogenesis of dyslexia.
“The molecular pathophysiology of dyslexia is less understood, but lines of evidence suggest that disruptions of neuronal migration and neurite outgrowth contribute importantly to the pathogenesis of the disease (Poelmans et al., 2011; Shao et al., 2016; Guidi et al., 2018).”
From Two Autism/Dyslexia Linked Variations of DOCK4 Disrupt the Gene Function on Rac1/Rap1 Activation, Neurite Outgrowth, and Synapse Development (2020) · cites this paper as Shao et al., 2016
Recent studies have identified DOCK4 variations associated with ASD, including single nucleotide variations and chromosome microdeletions or duplications.
“Recent studies have identified a number of DOCK4 variations associated with ASD, including both single nucleotide variations (SNVs) and chromosome microdeletions or duplications (Supplementary Table 1) 18–26.”
From Autism-like social deficit generated by Dock4 deficiency is rescued by restoration of Rac1 activity and NMDA receptor function. (2021) · cites this paper as [24]
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Disruption of functional networks in dyslexia: a whole-brain, data-driven analysis of connectivity
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Guo, D., Peng, Y., Wang, L., Sun, X., Wang, X., Liang, C., Yang, X., Li, S., Xu, J., Ye, W.-C., et al. (2021) · Molecular Psychiatry · doi:10.1038/s41380-019-0472-7 · Cited by 102 · see citing works
Huang, M., Liang, C., Li, S., Zhang, J., Guo, D., Zhao, B., Liu, Y., Peng, Y., Xu, J., Liu, W., et al. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00577 · Cited by 41 · see citing works
Self-citation
- Authors
- Shao, S., Kong, R., Zou, L., Zhong, R., Lou, J., Zhou, J., Guo, S., Wang, J., Zhang, X., Zhang, J., & Song, R.
- Affiliations
- Huazhong University of Science and Technology (CN)
- Maternal and Child Health Care Hospital of Bao'an (CN)
- University of South Carolina (US)
- Corresponding author
- Song, Ranran
- Venue
- Molecular Neurobiology
- Published
- 2015-07-17
- Volume
- 53
- Issue
- 6
- Pages
- 3967-3975
- ISSN
- 0893-7648 (ISSN-L)
- 1559-1182
- OpenAlex
- W1950161245
- Cited by
- 44
- References
- 1
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 5 · 2022: 7 · 2021: 5 · 2020: 5 · 2019: 5 · 2018: 4 · 2017: 6 · 2016: 3
- FWCI
- 10.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Molecular Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China
- Health and Family Planning Commission of Hubei Province
- Fundamental Research Funds for the Central Universities
- Topics
- Social Sciences › Psychology › Developmental and Educational Psychology › Reading and Literacy Development
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- developmental dyslexia, neuronal migration, neurite outgrowth, genetic risk variants, gene-gene interaction, DOCK4, KIAA0319, DCDC2, single nucleotide polymorphisms, Chinese population, neurodevelopmental disorders, genetic association studies, classification and regression trees
- MeSH terms
- Neuronal Outgrowth, Cell Movement, Child, Dyslexia, Epistasis, Genetic, Female, Humans, Male, Nerve Net, Neurons, Genetic Variation, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Genetic Association Studies
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