Estudo cl??nico e gen??tico de uma fam??lia com preval??ncia aumentada de sintomas obsessivos compulsivos

• Autor(a) principal: Silva, Daniele Oliveira Ferreira da
• Data de Publicação: 2019
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da UCB
• Texto Completo: https://bdtd.ucb.br:8443/jspui/handle/tede/2699
• topic: Exomas; Gen??tica; Transtorno obsessivo compulsivo; Obsessive compulsive disorder; Genetics; CNPQ::CIENCIAS DA SAUDE

Obsessive compulsive symptoms are common and often a disabling psychiatric condition, when in fact they configure the diagnosis of Obsessive-Compulsive Disorder (OCD). Such disease affects approximately 2% of the population and is associated with great personal, social and work disability, but if we consider the spectrum of disease with subclinical conditions, the prevalence tends to be higher. Several studies have shown that the etiology of obsessive-compulsive symptoms has a genetic component with recurrence rates ranging from 27% to 65%. From current genetic studies there are dozens of genes that may be related to OCD. We will study the families of ten siblings of the same father and mother where the prevalence of obsessive-compulsive symptoms is higher than in the general population: an initial trio of 3 individuals, a couple and a daughter, in which we have 2 members. already properly diagnosed with obsessive compulsive symptoms and OCD: father (one of ten siblings) and daughter. The daughter with symptoms since childhood. Following the search for 70 disease-related genes in the exomes of this trio, we will follow the study of the other brothers, spouses and their children. The hypothesis studied is the genetic relationship of the highest prevalence of obsessive-compulsive symptoms in this family with the most common markers identified with the disease and any new findings. The analysis of variants in the OCD-bearing father and the OCD-bearing daughter, but absent in the non-OCD mother, revealed 389 variations in 57 of the 70 most disease-related genes in the scientific literature. Only variants with the good quality criteria described above were considered in this analysis. From this grouping, we selected the 6 non-synonymous variables (with meaning), because they have the potential to alter the original amino acid sequence, generating mutation effect, to filter through the Sorting Intolerant From Tolerant (SIFT) and PolyPhen programs. For all variations analyzed, both programs resulted in the variations being neutral, so, they have no impact on the ability to alter expression of the genes studied. Extrapolation of Genomewide Association Studies (GWAS) findings in OCD to a family with a high prevalence of the disease is not possible, since more layers of knowledge are needed to explore this relationship.