Contribuição das microdeleções e microduplicações subteloméricas para o fenótipo dificuldade de aprendizagem na matemática

• Ano de defesa: 2016
• Autor(a) principal: Carolina de Castro Andrade Jorge
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais
• Palavras-chave em Português: Genética; Dificuldade de aprendizagem; Matemática; Deleção Cromossômica; Duplicação Cromossômica; Reação em Cadeia da Polimerase Multiplex
• Link de acesso: https://hdl.handle.net/1843/83516

Mathematics learning difficulty (MLD) is characterized by abnormally low Mathematical performance for age and schooling, which may be temporary or persistent, affecting 1 to 14% of school-age children. The impacts of school failure in Mathematics can negatively influence the individual's family, professional, social, emotional and intellectual context. MLD can be caused by environmental factors, such as low socioeconomic level, nutritional deficiency, elementary education, lack of motivation, lack of interest, teratogens, among others. In addition, a genetic, multifactorial etiology was suggested. Evidence for heterogeneity comes from the presence of MLD as part of genetic diseases, such as VelocardiofacialFacial Syndrome, Turner Syndrome, Fragile X Syndrome, Williams-Beuren Syndrome, among others. The presence of MLD in genetic syndromes suggests that changes in specific gene loci trigger this phenotype. There are few studies investigating the genetic bases of MLD in the literature, none investigating the contribution of subtelomeric microdeletions/microduplications. This is a population-based study, aiming at the inestigation of the association of subtelomeric microdeletions/microduplications and MLD in school children . The research was approved by COEP/UFMG. The sample consisted of 140 children with MLD, being Math learning difficulty (DAM) or Math and writing learning difficulties. The presence of subtelomeric microdeletions/microdulculations was investigated with the SALSA MLPA P070 kit. Three samples, the results of which were altered with this kit, also tested with the SALSA MLPA P036 kit and by SYBR Green PCR-HRM. Among the 140 cases investigated, a microdeletion of VAMP7 was detected in PAR2 (Xq28/Yq12); a duplication in S100B (21q22.3); and, a duplication in SECTM1 (17q25.3). Duplications of the S100B and SECTM1 genes were not confirmed with the SALSA MLPA P036 kit, because this kit does not present probes in these genes. However, they were confirmed by SYBR Green PCR-HRM. Deletion in VAMP7 was confirmed by both the SALSA MLPA P036 kit and by SYBR Green PCR-HRM. The frequency of CNVs in the VAMP7, S100B and SECTM1 genes in the general population was evaluated in a sample of normal individuals from Belo Horizonte by SYBR Green PCR-HRM. None showed a variation in the number of copies, despite three doubtful results (one per gene). These will be repeated. In advance, we can predict that a frequency of CNVs in VAMP7, S100B and SECTM1 is lower than 1% in the Belo Horizonte population. The search in CNV databases (DGV and DECIPHER) suggests that all three genes can be deleted/duplicated in both normal and affected individuals. VAMP7, S100B and SECTM1 are related to nervous system alterations and therefore can be considered candidates for cognitive deficits. S100B has been previously associated with dyslexia. The results reported here suggest that subtelomeric microdeletions/microduplications may be part of the genetic component of the etiology of the Mathematics learning difficulty.