Genetic Modifications of Developmental Dyslexia and Its Representation Using In Vivo, In Vitro Model

Abstract

Dyslexia is a genetic and heritable disorder that has yet to discover the treatment of it, especially at the molecular and drug intervention levels. This review provides an overview of the current findings on the environmental and genetic factors involved in developmental dyslexia. The latest techniques used in diagnosing the disease and macromolecular factors findings may contribute to a higher degree of development in detangling the proper management and treatment for dyslexic individuals. Furthermore, this review tried to put together all the models used in the current dyslexia research for references in future studies that include animal models as well as in vitro models and how the previous research has provided consistent data across many years and regions. Thus, we suggest furthering the studies using an organoid model based on the existing gene polymorphism, pathways, and neuronal function input.

Keywords

dyslexia - genetic of language disorder - developmental disorder

Ethics Approval and Consent to Participate

Not Applicable

Consent for publication

Not applicable.

Availability of Data and Material

Not applicable.

Authors' Contributions

Z.M.M.Z. conceptualized the idea and writings, original draft; S.A.A. idea, writing, review and editing; M.M.G. writing and editing; F.A.J. writing and editing.

Publikationsverlauf

Artikel online veröffentlicht:
27. Februar 2024

• References

• 1 Hall C, Dahl-Leonard K, Cho E. et al. Forty years of reading intervention research for elementary students with or at risk for dyslexia: a systematic review and meta-analysis. Read Res Q 2022; 58 (02) 285-312
• 2 Wolf M, Bowers PG. The double-deficit hypothesis for the development dyslexias. J Educ Psychol 1999; 91 (03) 415-438
• 3 Stein J. Theories about developmental dyslexia. Brain Sci 2023; 13 (02) 208
• 4 Wilson SM, Brambati SM, Henry RG. et al. The neural basis of surface dyslexia in semantic dementia. Brain 2009; 132 (Pt 1): 71-86
• 5 Démonet JF, Taylor MJ, Chaix Y. Developmental dyslexia. Lancet 2004; 363 (9419) 1451-1460
• 6 Caverzasi E, Mandelli ML, Hoeft F. et al. Abnormal age-related cortical folding and neurite morphology in children with developmental dyslexia. Neuroimage Clin 2018; 18: 814-821
• 7 Galaburda AM, Kemper TL. Cytoarchitectonic abnormalities in developmental dyslexia: a case study. Ann Neurol 1979; 6 (02) 94-100
• 8 Stein J. The current status of the magnocellular theory of developmental dyslexia. Neuropsychologia 2019; 130: 66-77
• 9 Jariabková K, Hugdahl K, Glós J. Immune disorders and handedness in dyslexic boys and their relatives. Scand J Psychol 1995; 36 (04) 355-362
• 10 Lubs HA, Rabin M, Feldman E. et al. Familial dyslexia: genetic and medical findings in eleven three-generation families. Ann Dyslexia 1993; 43 (01) 44-60
• 11 Olson RK. Dyslexia: nature and nurture. Dyslexia 2002; 8 (03) 143-159
• 12 Schumacher J, Hoffmann P, Schmäl C, Schulte-Körne G, Nöthen MM. Genetics of dyslexia: the evolving landscape. J Med Genet 2007; 44 (05) 289-297
• 13 Snowling MJ, Melby-Lervåg M. Oral language deficits in familial dyslexia: a meta-analysis and review. Psychol Bull 2016; 142 (05) 498-545
• 14 Raschle NM, Chang M, Gaab N. Structural brain alterations associated with dyslexia predate reading onset. Neuroimage 2011; 57 (03) 742-749
• 15 van Setten ERH, Maurits NM, Maassen BAM. N1 lateralization and dyslexia: an event-related potential study in children with a familial risk of dyslexia. Dyslexia 2019; 25 (01) 84-102
• 16 Raschle NM, Stering PL, Meissner SN, Gaab N. Altered neuronal response during rapid auditory processing and its relation to phonological processing in prereading children at familial risk for dyslexia. Cereb Cortex 2014; 24 (09) 2489-2501
• 17 Yu X, Ferradal S, Dunstan J. et al. Patterns of neural functional connectivity in infants at familial risk of developmental dyslexia. JAMA Netw Open 2022; 5 (10) e2236102
• 18 Kershner JR. Dyslexia as an adaptation to cortico-limbic stress system reactivity. Neurobiol Stress 2020; 12: 100223
• 19 Theodoridou D, Christodoulides P, Zakopoulou V, Syrrou M. Developmental dyslexia: environment matters. Brain Sci 2021; 11 (06) 782
• 20 Ece Demir-Lira Ö, Applebaum LR, Goldin-Meadow S, Levine SC. Parents' early book reading to children: Relation to children's later language and literacy outcomes controlling for other parent language input. Dev Sci 2019; 22 (03) e12764
• 21 Torppa M, Vasalampi K, Eklund K, Niemi P. Long-term effects of the home literacy environment on reading development: familial risk for dyslexia as a moderator. J Exp Child Psychol 2022; 215: 105314
• 22 Becker N, Vasconcelos M, Oliveira V. et al. Genetic and environmental risk factors for developmental dyslexia in children: systematic review of the last decade. Dev Neuropsychol 2017; 42 (7-8): 423-445
• 23 Liu L, Wang J, Shao S. et al. Descriptive epidemiology of prenatal and perinatal risk factors in a Chinese population with reading disorder. Sci Rep 2016; 6: 36697
• 24 Krafnick AJ, Flowers DL, Luetje MM, Napoliello EM, Eden GF. An investigation into the origin of anatomical differences in dyslexia. J Neurosci 2014; 34 (03) 901-908
• 25 Kujala T, Thiede A, Palo-oja P. et al. Brain structures associated with reading and their abnormalities in dyslexia: a whole brain analysis. Cold Spring Harbour preprint. 2020;
• 26 Kujala T, Sihvonen AJ, Thiede A. et al. Voxel and surface based whole brain analysis shows reading skill associated grey matter abnormalities in dyslexia. Sci Rep 2021; 11 (01) 10862
• 27 Bailey SK, Aboud KS, Nguyen TQ, Cutting LE. Applying a network framework to the neurobiology of reading and dyslexia. J Neurodev Disord 2018; 10 (01) 37
• 28 Perrino PA, Chasse RY, Monaco AP, Molnár Z, Velayos-Baeza A, Fitch RH. Rapid auditory processing and medial geniculate nucleus anomalies in Kiaa0319 knockout mice. Genes Brain Behav 2022; 21 (06) e12808
• 29 Liebig J, Friederici AD, Neef NE. LEGASCREEN Consortium. Auditory brainstem measures and genotyping boost the prediction of literacy: a longitudinal study on early markers of dyslexia. Dev Cogn Neurosci 2020; 46: 100869 . Erratum in: Dev Cogn Neurosci 2021;48:100889
• 30 Brandler WM, Paracchini S. The genetic relationship between handedness and neurodevelopmental disorders. Trends Mol Med 2014; 20 (02) 83-90
• 31 Pinel P, Fauchereau F, Moreno A. et al. Genetic variants of FOXP2 and KIAA0319/TTRAP/THEM2 locus are associated with altered brain activation in distinct language-related regions. J Neurosci 2012; 32 (03) 817-825
• 32 Schmitz J, Kumsta R, Moser D, Güntürkün O, Ocklenburg S. KIAA0319 promoter DNA methylation predicts dichotic listening performance in forced-attention conditions. Behav Brain Res 2018; 337: 1-7
• 33 Mascheretti S, Trezzi V, Giorda R. et al. Complex effects of dyslexia risk factors account for ADHD traits: evidence from two independent samples. J Child Psychol Psychiatry 2017; 58 (01) 75-82
• 34 Fisher SE, DeFries JC. Developmental dyslexia: genetic dissection of a complex cognitive trait. Nat Rev Neurosci 2002; 3 (10) 767-780
• 35 McGrath LM, Smith SD, Pennington BF. Breakthroughs in the search for dyslexia candidate genes. Trends Mol Med 2006; 12 (07) 333-341
• 36 Kere J. Molecular genetics and molecular biology of dyslexia. Wiley Interdiscip Rev Cogn Sci 2011; 2 (04) 441-448
• 37 Peterson RL, Pennington BF. Developmental dyslexia. Annu Rev Clin Psychol 2015; 11: 283-307
• 38 Doust C, Fontanillas P, Eising E. et al; 23andMe Research Team, Quantitative Trait Working Group of the GenLang Consortium. Discovery of 42 genome-wide significant loci associated with dyslexia. Nat Genet 2022; 54 (11) 1621-1629
• 39 Galaburda AM. Animal models of developmental dyslexia. Front Neurosci 2022; 16: 981801
• 40 Guidi LG, Mattley J, Martinez-Garay I. et al. Knockout mice for dyslexia susceptibility gene homologs KIAA0319 and KIAA0319L have unaffected neuronal migration but display abnormal auditory processing. Cereb Cortex 2017; 27 (12) 5831-5845
• 41 Gabel LA, Marin I, LoTurco JJ. et al. Mutation of the dyslexia-associated gene Dcdc2 impairs LTM and visuo-spatial performance in mice. Genes Brain Behav 2011; 10 (08) 868-875
• 42 Gabel LA, Voss K, Johnson E. et al. Identifying dyslexia: link between maze learning and dyslexia susceptibility gene, DCDC2, in young children. Dev Neurosci 2021; 43 (02) 116-133
• 43 Andrews W, Liapi A, Plachez C. et al. Robo1 regulates the development of major axon tracts and interneuron migration in the forebrain. Development 2006; 133 (11) 2243-2252
• 44 Price KM, Wigg KG, Eising E. et al; Quantitative Trait Working Group of the GenLang Consortium. Hypothesis-driven genome-wide association studies provide novel insights into genetics of reading disabilities. Transl Psychiatry 2022; 12 (01) 495
• 45 Dasgupta A, Amack JD. Cilia in vertebrate left-right patterning. Philos Trans R Soc Lond B Biol Sci 2016; 371 (1710) 20150410
• 46 Fitch WT. Empirical approaches to the study of language evolution. Psychon Bull Rev 2017; 24 (01) 3-33
• 47 Kirby S. Culture and biology in the origins of linguistic structure. Psychon Bull Rev 2017; 24 (01) 118-137
• 48 Paniagua S, Cakir B, Hu Y. et al. Dyslexia associated gene KIAA0319 regulates cell cycle during human neuroepithelial cell development. Front Cell Dev Biol 2022; 10: 967147
• 49 Diaz R, Kronenberg NM, Martinelli A. et al. KIAA0319 influences cilia length, cell migration and mechanical cell-substrate interaction. Sci Rep 2022; 12 (01) 722
• 50 Levecque C, Velayos-Baeza A, Holloway ZG, Monaco AP. The dyslexia-associated protein KIAA0319 interacts with adaptor protein 2 and follows the classical clathrin-mediated endocytosis pathway. Am J Physiol Cell Physiol 2009; 297 (01) C160-C168
• 51 Tammimies K, Bieder A, Lauter G. et al. Ciliary dyslexia candidate genes DYX1C1 and DCDC2 are regulated by regulatory factor X (RFX) transcription factors through X-box promoter motifs. FASEB J 2016; 30 (10) 3578-3587
• 52 Bieder A, Yoshihara M, Katayama S. et al. Dyslexia candidate gene and ciliary gene expression dynamics during human neuronal differentiation. Mol Neurobiol 2020; 57 (07) 2944-2958
• 53 Tapia-Páez I, Tammimies K, Massinen S, Roy AL, Kere J. The complex of TFII-I, PARP1, and SFPQ proteins regulates the DYX1C1 gene implicated in neuronal migration and dyslexia. FASEB J 2008; 22 (08) 3001-3009
• 54 Massinen S, Hokkanen ME, Matsson H. et al. Increased expression of the dyslexia candidate gene DCDC2 affects length and signaling of primary cilia in neurons. PLoS One 2011; 6 (06) e20580
• 55 Huang M, Liang C, Li S. et al. Two autism/dyslexia linked variations of DOCK4 disrupt the gene function on Rac1/Rap1 activation, neurite outgrowth, and synapse development. Front Cell Neurosci 2020; 13: 577
• 56 Massinen S, Wang J, Laivuori K. et al. Genomic sequencing of a dyslexia susceptibility haplotype encompassing ROBO1. J Neurodev Disord 2016; 8: 4
• 57 Wang L, Owusu-Hammond C, Sievert D, Gleeson JG. Stem cell-based organoid models of neurodevelopmental disorders. Biol Psychiatry 2023; 93 (07) 622-631
• 58 Eising E, Mirza-Schreiber N, de Zeeuw EL. et al. Genome-wide analyses of individual differences in quantitatively assessed reading- and language-related skills in up to 34,000 people. Proc Natl Acad Sci U S A 2022; 119 (35) e2202764119
• 59 Venkatesh SK, Siddaiah A, Padakannaya P, Ramachandra NB. Association of SNPs of DYX1C1 with developmental dyslexia in an Indian population. Psychiatr Genet 2014; 24 (01) 10-20
• 60 Gialluisi A, Andlauer TFM, Mirza-Schreiber N. et al. Genome-wide association study reveals new insights into the heritability and genetic correlates of developmental dyslexia. Mol Psychiatry 2021; 26 (07) 3004-3017
• 61 Sun X, Song S, Liang X. et al. ROBO1 polymorphisms, callosal connectivity, and reading skills. Hum Brain Mapp 2017; 38 (05) 2616-2626
• 62 Paracchini S, Ang QW, Stanley FJ, Monaco AP, Pennell CE, Whitehouse AJO. Analysis of dyslexia candidate genes in the Raine cohort representing the general Australian population. Genes Brain Behav 2011; 10 (02) 158-165
• 63 Massinen S, Tammimies K, Tapia-Páez I. et al. Functional interaction of DYX1C1 with estrogen receptors suggests involvement of hormonal pathways in dyslexia. Hum Mol Genet 2009; 18 (15) 2802-2812
• 64 Tarkar A, Loges NT, Slagle CE. et al; UK10K. DYX1C1 is required for axonemal dynein assembly and ciliary motility. Nat Genet 2013; 45 (09) 995-1003
• 65 Gonda Y, Andrews WD, Tabata H. et al. Robo1 regulates the migration and laminar distribution of upper-layer pyramidal neurons of the cerebral cortex. Cereb Cortex 2013; 23 (06) 1495-1508
• 66 Gonda Y, Namba T, Hanashima C. Beyond axon guidance: roles of slit-robo signaling in neocortical formation. Front Cell Dev Biol 2020; 8: 607415
• 67 Burbridge TJ, Wang Y, Volz AJ. et al. Postnatal analysis of the effect of embryonic knockdown and overexpression of candidate dyslexia susceptibility gene homolog Dcdc2 in the rat. Neuroscience 2008; 152 (03) 723-733
• 68 Darki F, Peyrard-Janvid M, Matsson H, Kere J, Klingberg T. Three dyslexia susceptibility genes, DYX1C1, DCDC2, and KIAA0319, affect temporo-parietal white matter structure. Biol Psychiatry 2012; 72 (08) 671-676
• 69 Gostic M, Martinelli A, Tucker C. et al. The dyslexia susceptibility KIAA0319 gene shows a specific expression pattern during zebrafish development supporting a role beyond neuronal migration. J Comp Neurol 2019; 527 (16) 2634-2643