65ª Reunião Anual da SBPC

D. Ciências da Saúde - 7. Fonoaudiologia - 1. Fonoaudiologia

CANDIDATE GENES FOR SUSCEPTIBILITY OF DEVELOPMENTAL DYSLEXIA - A SYSTEMATIC REVIEW

Thaís dos Santos Gonçalves - Faculdade de Odontologia de Bauru - FOB-USP Patrícia Abreu Pinheiro Crenitte - Faculdade de Odontologia de Bauru - FOB-USP

INTRODUÇÃO:

Developmental dyslexia (DD) or Reading Disability (RD) is the most common learning disorder that affects approximately 5 to 17 % of school-aged children, however, their exact causal mechanisms are beginning to be known recently. Studies suggest that dyslexia is a heritable disorder. Yet, 75 % of the phenotypic variance can be explained by genetic component. Until now were identified at least 11 risk loci involved in the susceptibility of dyslexia, including 2q22.3, 7q32, 11q13.4, DYX1 to DYX6, DYX8, and DYX9. Most of the identified dyslexia candidate genes by linkage analysis and association studies were integrated into a theoretical molecular signaling network responsible for regulating neuronal migration. Although the associated candidate genes with risk of dyslexia have been described in the literature, the results of many studies still show controversies between genes and the manifestations of dyslexia.

OBJETIVO DO TRABALHO:

To investigate the most related genes with dyslexia described in the literature in the last 5 years.

MÉTODOS:

The methodology adopted to meet the objective was the systematically review of the literature. Were consulted online electronic databases (PubMed, ISI Web of Science and Scielo), and were searched papers latest five years until February 2013, using the search terms “dyslexia” and “genetic”. Studies eligible for inclusion in systematic review had to fulfill the criteria: (1) case–control study or Trait Disequilibrium Test (TDT) family design, (2) confirmed diagnostic of dyslexia. Were excluded no control population, duplicate of previous publication, animal studies, reviews, and unpublished reports. The following information was extracted from the eligible studies: first author's surname, year of publication, study population, design type, sample size, studied genes or loci and the result of the research.

RESULTADOS E DISCUSSÃO:

After an extensive search, a total of 132 potentially relevant publications about genetic of dyslexia, only 28 publications met the inclusion criteria. Most of the found studies (16 studies - 57%) are concentrated in Germany and England. There is no published work with the population of South America. Were found studies of the following genes: ZNF804A and MRPL19/C2ORF3 (chromosome 2) and CNTNAP2 ROBO1 (Chromosome 3); DCDC2, KIAA0319, TTRAP and THEM2 (Chromosome 6); FOXP2 and DGKI (chromosome 7); GRIN2B (chromosome 12 ); VMP (NRSN1) (chromosome 13), and CYP19A1 DYX1C1 (chromosome 15); CMIP and ATP2C2 (chromosome 16); MC5R, DYM and NEDD4L (chromosome 18). Thus, the most studied gene was DCDC2 (10 studies), and that 7 found no association of the gene with dyslexia, 3 found this association. The second most studied gene was the KIAA0319 (7 studies), and that 5 found association with dyslexia and only 2 not found. The third most studied gene is the DYX1C1 (6 studies), and that 3 found association with dyslexia and 3 not found. Then, with two studies are ZNF804A genes (both found association with dyslexia) and CMIP (one study found the association and the other not found). The remaining genes had only 1 study, and was found association with dyslexia in the FOXP2 gene, DGKI, GRIN2B, CYP19A1, MC5R, DYM and NEDD4L, and no association with dyslexia genes in MRPL19/C2ORF3, ROBO1, CNTNAP2, TTRAP, THEM2 , VMP (NRSN1) and ATP2C2.

CONCLUSÕES:

Then, in this study, it was found that KIAA0319 gene shows the most consistent evidence of linkage for DD. This study found discrepancies in the results of studies in most genes studied. The analysis accuracy (and reproducibility) of these data is limited by the difficulty inherent in the definition, evaluation and characterization of the DD phenotype, the small sample sizes available for this type of analysis, the genetic heterogeneity of the population and the limitations of the statistical methods used. However, is necessary more studies with a lager sample size in an independent population. And for consistent results, these issues should be reflected in the methodology of future studies.

Palavras-chave: dyslexia, candidate genes, learning disabilities.