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https://revistacefac.org.br/article/doi/10.1590/1982-0216/20232528722
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Genetic recurrence and molecular markers of dyslexia in the Brazilian population

Thais dos Santos Gonçalves; Thais Freire; Thiago José Dionísio; Ricardo Franco de Lima; Lucimara Teixeira das Neves; Carlos Ferreira dos Santos; Patrícia Abreu Pinheiro Crenitte

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Abstract

Purpose: to investigate genetic recurrence and molecular markers for dyslexia in two candidate genes in the Brazilian population.

Methods: a cross-sectional, case-control, observational study, with five single nucleotide polymorphisms (SNPs) studied in DYX1C1 and KIAA0319 genes in 86 subjects with dyslexia and 66 controls, matched for gender and age. SNPs were genotyped using the polymerase chain reaction technique in real time, and distribution of genotypic and allelic frequencies between the groups was analyzed.

Results: it was determined that 68% of the subjects with dyslexia present a family history of learning difficulties. The DYX1C1 gene did not demonstrate an association with dyslexia, which was found regarding the rs9461045 marker of the KIAA0319 gene.

Conclusion: a family history of learning problems was present in more than two-thirds of the group with dyslexia, indicating that this is an important risk factor. An association with dyslexia in the rs9461045 marker was noted, making the study the first one to show an association of the KIAA0319 gene with dyslexia, in Latin America.

Keywords

Dyslexia, Heredity, Endophenotypes, Genetics

Referências

1. Paracchini S, Thomas A, Castro S, Lai C, Paramasivam M, Wang Y et al. The chromosome 6p22 haplotype associated with dyslexia reduces the expression of KIAA0319, a novel gene involved in neuronal migration. Hum Mol Genet. 2006;15(10):1659-66. https://doi.org/10.1093/hmg/ddl089. PMID: 16600991.

2. Schumacher J, Hoffmann P, Schmäl C, Schulte-Körne G, Nöthen MM. Genetics of dyslexia: the evolving landscape. J Med Genet. 2007;44(5):289-97. https://doi.org/10.1136/jmg.2006.046516. PMID: 17307837.

3. Dennis MY, Paracchini S, Scerri TS, Prokunina-Olsson L, Knight JC, Wade-Martins R et al. A common variant associated with dyslexia reduces expression of the KIAA0319 gene. PLoS Genet. 2009;5(3):e1000436. https://doi.org/10.1371/journal.pgen.1000436. PMID: 19325871.

4. Démonet JF, Taylor MJ, Chaix Y. Developmental dyslexia. Lancet. 2004;363(9419):1451-60. https://doi.org/10.1016/S0140-6736(04)16106-0. PMID: 15121410.

5. Grigorenko EL, Wood FB, Meyer MS, Hart LA, Speed WC, Shuster A et al. Continuing the search for dyslexia genes on 6p. Am J Med Genet B Neuropsychiatr Genet. 2003;118B(1):89-98. https://doi.org/10.1002/ajmg.b.10032. PMID: 12627473.

6. Fisher SE, Francks C. Genes, cognition and dyslexia: learning to read the genome. Trends Cogn Sci. 2006;10(6):250-7. https://doi.org/10.1016/j.tics.2006.04.003. PMID: 16675285.

7. Paracchini S, Scerri T, Monaco AP. The genetic lexicon of dyslexia. Annu Rev Genomics Hum Genet. 2007;8:57-79. https://doi.org/10.1146/annurev.genom.8.080706.092312. PMID: 17444811.

8. Taipale M, Kaminen N, Nopola-Hemmi J, Haltia T, Myllyluoma B, Lyytinen H et al. A candidate gene for developmental dyslexia encodes a nuclear tetratricopeptide repeat domain protein dynamically regulated in brain. Proc Natl Acad Sci USA. 2003;100(20):11553-8. https://doi.org/10.1073/pnas.1833911100. PMID: 12954984.

9. Francks C, Paracchini S, Smith SD, Richardson AJ, Scerri TS, Cardon LR et al. A 77-kilobase region of chromosome 6p22.2 is associated with dyslexia in families from the United Kingdom and from the United States. Am J Hum Genet. 2004;75(6):1046-58. https://doi.org/10.1086/426404. PMID: 15514892.

10. Cope N, Harold D, Hill G, Moskvina V, Stevenson J, Holmans P et al. Strong evidence that KIAA0319 on chromosome 6p is a susceptibility gene for developmental dyslexia. Am J Hum Genet. 2005;76(4):581-91. https://doi.org/10.1086/429131. PMID: 15717286.

11. Meng H, Smith SD, Hager K, Held M, Liu J, Olson RK. DCDC2 is associated with reading disability and modulates neuronal development in the brain. Proc Natl Acad Sci USA. 2005;102(47):17053-8. https://doi.org/10.1073/pnas.0508591102. PMID: 16278297.

12. Couto JM, Gomez L, Wigg K, Cate-Carter T, Archibald J, Anderson B et al. The KIAA0319-like (KIAA0319L) gene on chromosome 1p34 as a candidate for reading disabilities. J Neurogenet. 2008;22(4):295-313. https://doi.org/10.1080/01677060802354328. PMID: 19085271.

13. Hannula-Jouppi K, Kaminen-Ahola N, Taipale M, Eklund R, Nopola-Hemmi J, Kääriäinen H et al. The axon guidance receptor gene ROBO1 is a candidate gene for developmental dyslexia. PLoS Genet. 2005;1(4):e50. https://doi.org/10.1371/journal.pgen.0010050. PMID: 16254601.

14. Anthoni H, Zucchelli M, Matsson H, Müller-Myhsok B, Fransson I, Schumacher J et al. A locus on 2p12 containing the co-regulated MRPL19 and C2ORF3 genes is associated to dyslexia. Hum Mol Genet. 2007;16(6):667-77. https://doi.org/10.1093/hmg/ddm009. PMID: 17309879.

15. Olson RK. Dyslexia: nature and nurture. Dyslexia. 2002;8(3):143-59. https://doi.org/10.1002/dys.228. PMID: 12222731.

16. Marlow AJ, Fisher SE, Francks C, MacPhie IL, Cherny SS, Richardson AJ et al. Use of multivariate linkage analysis for dissection of a complex cognitive trait. Am J Hum Genet. 2003;72(3):561-70. https://doi.org/10.1086/368201. PMID: 12587094.

17. Goodwin W. An introduction to forensic genetics. Chichester: John Wiley & sons; 2007.

18. Bouchard TJ. Genetic influence on human psychological traits: a survey. Curr Dir Psychol Sci. 2004;13(4)148-51. https://doi.org/10.1111/j.0963-7214.2004.00295.x.

19. Burton PR, Tobin MD, Hopper JL. Series: genetic epidemiology 1. Key concepts in genetic epidemiology. Lancet. 2005;366(9489):941-51. https://doi.org/10.1016/S0140-6736(05)67322-9. PMID: 16154023.

20. Deffenbacher KE, Kenyon JB, Hoover DM, Olson RK, Pennington BF, DeFries JC et al. Refinement of the 6p21.3 quantitative trait locus influencing dyslexia: linkage and association analyses. Hum Genet. 2004;115(2):128-38. https://doi.org/10.1007/s00439-004-1126-6. PMID: 15138886.

21. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th Edition. Washington, DC: American Psychiatric Press, Inc.; 2013.

22. Capellini AS, Oliveira AM, Cuetos F. Provas de avaliação dos processos de leitura (PROLEC). São Paulo: Casa do Psicólogo, 2010.

23. Solé X, Guinó E, Valls J, Iniesta R, Moreno V. SNPStats: a web tool for the analysis of association studies. Bioinformatics. 2006;22(15):1928-9. https://doi.org/10.1093/bioinformatics/btl26. PMID: 16720584.

24. Baillieux H, Vandervliet EJ, Manto M, Parizel PM, De Deyn PP, Mariën P. Developmental dyslexia and widespread activation across the cerebellar hemispheres. Brain Lang. 2009;108(2):122-32. https://doi.org/10.1016/j.bandl.2008.10.001. PMID: 18986695.

25. Lima RF, Salgado CA, Cyasca SM. Dificuldades de aprendizagem: queixas escolares e diagnósticos em um Serviço de Neurologia Infantil. Rev Neurocien. 2006;14(4):185-90. https://doi.org/10.34024/rnc.2006.v14.8741.

26. Brambati SM, Termine C, Ruffino M, Danna M, Lanzi G, Stella G et al. Neuropsychological deficits and neural dysfunction in familial dyslexia. Brain Research. 2006;1113(1):174-85. https://doi.org/10.1016/j.brainres.2006.06.099. PMID: 16934234.

27. Scerri TS, Paracchini S, Morris A, MacPhie IL, Talcott J, Stein J et al. Identification of candidate genes for dyslexia susceptibility on chromosome 18. PLoS One. 2010;5(10):e13712. https://doi.org/10.1371/journal.pone.0013712. PMID: 21060895.

28. Hawke JL, Wadsworth SJ, DeFries JC. Genetic influences on reading difficulties in boys and girls: the Colorado twin study. Dyslexia. 2006;12(1):21-9. https://doi.org/10.1002/dys.301. PMID: 16512171.

29. Zhao H, Chen Y, Zhang B, Zuo P. KIAA0319 gene polymorphisms are associated with developmental dyslexia in Chinese Uyghur children. J Hum Genet. 2016;61(8):745-52. https://doi.org/10.1038/jhg.2016.40. PMID: 27098879.

30. Velayos-Baeza A, Levecque C, Kobayashi K, Holloway ZG, Monaco AP. The dyslexia-associated KIAA0319 protein undergoes proteolytic processing with {gamma}-secretase-independent intramembrane cleavage. J Biol Chem. 2010;285(51):40148-62. https://doi.org/10.1074/jbc.M110.145961. PMID: 20943657.

31. Venkatesh SK, Siddaiah A, Padakannaya P, Ramachandra NB. Analysis of genetic variants of dyslexia candidate genes KIAA0319 and DCDC2 in Indian population. J Hum Genet. 2013;58:531-8. https://doi.org/10.1038/jhg.2013.46. PMID: 23677054.

32. Sun Y, Gao Y, Zhou Y, Chen H, Wang G, Xu J et al. Association study of developmental dyslexia candidate genes DCDC2 and KIAA0319 in Chinese population. Am J Med Genet B Neuropsychiatr Genet. 2014;165B(8):627-34. https://doi.org/10.1002/ajmg.b.32267. PMID: 25230923.

33. Luciano M, Lind PA, Duffy DL, Castles A, Wright MJ, Montgomery GW et al. A haplotype spanning KIAA0319 and TTRAP is associated with normal variation in reading and spelling ability. Biol Psychiatry. 2007;62(7):811-7. https://doi.org/10.1016/j.biopsych.2007.03.007. PMID: 17597587.

34. Skeide MA, Evans TM, Mei EZ, Abrams DA, Menon V. NRSN1 associated grey matter volume of the visual word form area reveals dyslexia before school. Brain. 2016;139(10):2792-803. https://doi.org/10.1093/brain/aww153.

35. Müller B, Wilcke A, Czepezauer I, Ahnert P, Boltze J, Kirsten H. Association, characterisation and meta-analysis of SNPs linked to general reading ability in a German dyslexia case-control cohort. Scientific Reports. 2016;6(27901):1-11. https://doi.org/10.1038/srep27901. PMID: 27312598.

36. Eicher JD, Montgomery AM, Akshoomoff N, Amaral DG, Bloss CS, Libiger O et al. Dyslexia and language impairment associated genetic markers influence cortical thickness and white matter in typically developing children. Brain Imaging Behav. 2016;10:272-82. https://doi.org/10.1007/s11682-015-9392-6. PMID: 25953057.

37. Shao S, Niu Y, Zhang X, Kong R, Wang J, Liu L et al. Opposite associations between individual KIAA0319 polymorphisms and developmental dyslexia risk across populations: a stratified meta-analysis by the study population. Scientifd Reports. 2016;6:30454. https://doi.org/10.1038/srep30454. PMID: 27464509.

38. Venkatesh SK, Siddaiah A, Padakannaya P, Ramachandra NB. An examination of candidate gene SNPs for dyslexia in an Indian sample. Behav Genet. 2011;41(1):105-9. https://doi.org/10.1007/s10519-010-9441-2. PMID: 21203818.

39. Wigg KG, Couto JM, Feng Y, Anderson B, Cate-Carter TD, Macciardi F et al. Support for EKN1 as the susceptibility locus for dyslexia on 15q21. Mol Psychiatry. 2004;9(12):1111-21. https://doi.org/10.1038/sj.mp.4001543. PMID: 15249932.

40. Svidnicki M, Lima RF, Salgado CA. Study of candidate genes for dyslexia in Brazilian individuals. Genet Mol Res. 2013;12(4):5356-64. https://doi.org/10.4238/2013. PMID: 24301907.

41. Gialluisi A, Andlauer TFM, Mirza-Schreiber N, Moll K, Becker J, Hoffmann P et al. Genome-wide association study reveals new insights into the heritability and genetic correlates of developmental dyslexia. Mol Psychiatry. 2021;26(7):3004-17. https://doi.org/10.1038/s41380-020-00898-x. PMID: 33057169.

42. Erbeli F, Rice M, Paracchini S. Insights into dyslexia genetics research from the last two decades. Brain Sci. 2022;12(1):27. https://doi.org/10.3390/brainsci12010027. PMID: 35053771.
 


Submetido em:
03/11/2022

Aceito em:
22/12/2022

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