Análise de genes envolvidos na neurotransmissão, formação e manutenção sináptica em indivíduos com transtornos do espectro do Autismo

• Ano de defesa: 2014
• Autor(a) principal: Martins, Ana Luiza Bossolani [UNESP]
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Estadual Paulista (Unesp)
• Palavras-chave em Português: Genetica humana; Sinapse - Aspectos genéticos; Variações do número de cópias de DNA; Transmissão nervosa; Transtornos do espectro do autismo Aspectos genéticos; Human genetics
• Link de acesso: http://hdl.handle.net/11449/122182

Even with all of molecular evolution research strategies, the etiology of Autism Spectrum Disorders (ASD) is still widely debated, due to its complexity and variation. These are disorders that manifest in the first three years of life, characterized by changes in communication, socialization, repetitive and stereotypic behavior, isolated or associated with birth defects, genetic disorders or other conditions. In individuals with these behavioral changes, dysmorphic or not dysmorphic, changes have been described in all chromosomes and genes proposed there as candidates to be involved in the pathogenesis. There are reports of cases with changes such as mutations and Copy Number Variations (CNVs) involving genes expressed in the central nervous system. This study investigated by MLPA (Multiplex Ligation-dependent Probe Amplification), CNVs and mutations in synaptic genes UBE3A, GRM5, DLGAP2, NEDD4, NRXN1, CASP3, MAGI2, SHANK1, SHANK2 and PTEN, which are also involved in the formation, maintenance and synaptic neurotransmission. Also indirectly investigated other possible genes and gene regions being investigated by commercial kits. The 300 individuals with the Autism Spectrum Disorders were studied and found 23 (8%) with alterations in eight of the ten selected genes, beyond three others regions as PTENP1, KLLN and 16p11.2. No alterations in UBE3A, PTEN and SHANK1 genes were observed. No patient had more than one alteration. When possible, to investigate the alteration in the parents was performed to determine whether they were inherited or de novo. In some cases the genotypic and phenotypic findings could be directly related. The data showed that mutations, duplications, but especially exonic deletions are not uncommon in autistic events and seem to participate in the pathogenesis of this psychiatric disorder. These alterations may contribute to the predisposition to ASD