O Papel da variação do número de cópias genômicas no fenótipo clínico de deficiência intelectual em uma coorte retrospectiva da rede pública de saúde do Estado de Goiás
| dc.contributor.advisor-co1 | Silva, Daniela de Melo e | |
| dc.contributor.advisor1 | Cruz, Aparecido Divino da | |
| dc.contributor.advisor1Lattes | http://lattes.cnpq.br/7868817504129985 | por |
| dc.creator | Pereira, Rodrigo Roncato | |
| dc.creator.Lattes | http://lattes.cnpq.br/3086398842804414 | por |
| dc.date.accessioned | 2014-09-18T21:39:12Z | |
| dc.date.issued | 2014-03-31 | |
| dc.description.abstract | Intellectual disability is a signal comprising a set of clinically and genetically heterogeneous disorders in which the development and/or function of the brain is compromised. This deficiency is characterized by significant limitations both in intellectual functioning and in adaptive behavior and is observed begins before 18 years of age. It is characterized by a high degree of variable expression, and the expression of a wide range of phenotypes, ranging from various genetic syndromes known to characteristics non-syndromic and psychological and/or psychiatric disorders. The etiology is still poorly understood and about half of the cases are unclear. In recent years, the chromosomal analysis by microarray has revolutionized the evaluation of patients with developmental delay or intellectual disability. By this method, the genome of a patient is examined to detect gains or losses of genetic material that are usually too small to be detected by chromosome banding studies. Genomic deletions and duplications have an important role in characterizing genetic diseases, including many neurological disorders and neural development. Identifying these changes may contribute to the clinical management of affected individuals and assist their families, and furthermore, can provide information on the processes of development and brain function. In this context the main objective of this study was identified possible submicroscopic genomic changes associated with intellectual disability, using a platform Chromosomal Microarray high resolution in patients referred by doctors of public health from Goiás state and had initially a normal karyotype. Thus 15 patients with intellectual disabilities were tested by high resolution HD CytoScan Array (Affymetrix) tecnology which detected the presence of 33 variations in the number of genome copies in 10 (66.7%) of the probands. Nineteen microduplications (57.6%) and 14 microdeletions (42.4%) were observed, and 17 CNVs (51.5%) were neutral, 7 (21.2%) pathogenic, 5 (15.15%) potentially pathogenic and 4 (12.12%) of uncertain significance. Five patients showed no change in the number of copies. In this study, we could propose a genetic etiology for the phenotype of 8 patients and thus the diagnostic yield of the platform used was 53.3%. Although modest, this study was significant because this technology was first employed in the state of Goiás and thus, could contribute more genetic information about this complex and heterogeneous neurological sign of great importance to global public health. | eng |
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| dc.description.resumo | A deficiência intelectual é um sinal que compreende um conjunto de distúrbios clinica e geneticamente heterogêneos em que o desenvolvimento e/ou a função do cérebro é comprometida. Esta deficiência é caracterizada por limitações significativas tanto no funcionamento intelectual quanto no comportamento adaptativo e se inicia antes dos 18 anos de idade. É caracterizada por um elevado grau de expressividade variável, e pela manifestação de uma grande gama de fenótipos, variando de diversas síndromes genéticas conhecidas a características não sindrômicas e desordens psicológicas e/ou psiquiátricas. A etiologia ainda é mal compreendida e cerca de metade dos casos não são esclarecidos. A análise cromossômica por microarray tem revolucionado, nos últimos anos, a avaliação de pacientes com atraso no desenvolvimento ou deficiência intelectual. Por este método, o genoma de um paciente é examinado para a detecção de ganhos ou perdas de material genético que, normalmente, são muito pequeno para serem detectados por estudos cromossômicos com bandamento G. Deleções e duplicações genômicas têm um papel importante na caracterização de doenças genéticas, incluindo muitas desordens neurológicas e do desenvolvimento neural. A identificação dessas alterações pode contribuir para a manejo clínico dos indivíduos afetados e auxiliar suas famílias, e além disso, pode também fornecer informações sobre os processos do desenvolvimento e funcionamento do cérebro. Neste contexto o objetivo principal deste estudo foi identificar possíveis alterações genômicas submicroscópicas associadas à deficiência intelectual, utilizando uma plataforma de Chromosomal Microarray de alta resolução, em pacientes referenciados por médicos da rede pública de saúde do Estado de Goiás e que tenham apresentado inicialmente um cariótipo normal. Desta forma foram testados 15 pacientes com deficiência intelectual, pela tecnologia de alta resolução CytoScan HD Array (Affymetrix) que detectou a presença de 33 variações no número de cópias genômicas em 10 (66,7%) dos probandos. Foram observadas 19 microduplicações (57,6%) e 14 microdeleções (42,4%), sendo que 17 CNVs (51,5%) eram neutras, 7 (21,2 %) patogênicas, 5 (15,15%) potencialmente patogênicas e 4 (12,12%) de significado incerto. Cinco pacientes não apresentaram nenhuma alteração no número de cópias. Neste estudo foi possível propor uma etiologia genética para o fenótipo de 8 pacientes e dessa forma o rendimento diagnóstico, a título de pesquisa, da plataforma utilizada foi de 53,3%. Este estudo foi relevante já que esta tecnologia foi empregada pela primeira vez no estado de Goiás e com isso, pudemos contribuir com mais informação genética sobre esse complexo e heterogêneo sinal neurológico de grande importância para a saúde pública mundial. | por |
| dc.description.sponsorship | Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES | por |
| dc.description.sponsorship | Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq | por |
| dc.format | application/pdf | * |
| dc.identifier.citation | Pereira, Rodrigo Roncato. O Papel da variação do número de cópias genômicas no fenótipo clínico de deficiência intelectual em uma coorte retrospectiva da rede pública de saúde do Estado de Goiás. 2014. 118 f. Tese (Doutorado em Biologia) - Programa de Pós-graduação em Biologia (ICB) - Universidade Federal de Goiás, Goiânia, 2014. | por |
| dc.identifier.uri | http://repositorio.bc.ufg.br/tede/handle/tede/3093 | |
| dc.language | por | por |
| dc.publisher | Universidade Federal de Goiás | por |
| dc.publisher.country | Brasil | por |
| dc.publisher.department | Instituto de Ciências Biológicas - ICB (RG) | por |
| dc.publisher.initials | UFG | por |
| dc.publisher.program | Programa de Pós-graduação em Biologia (ICB) | por |
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| dc.rights | Acesso Aberto | por |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
| dc.subject | Chromosomal Microarrays | por |
| dc.subject | Deficiência Intelectual | por |
| dc.subject | CNVs | por |
| dc.subject | Cariótipo | por |
| dc.subject | Intellectual Disabilities | eng |
| dc.subject | Karyotype | eng |
| dc.subject.cnpq | MICROBIOLOGIA::MICROBIOLOGIA APLICADA | por |
| dc.thumbnail.url | http://repositorio.bc.ufg.br/tede/retrieve/7932/merged.pdf.jpg | * |
| dc.title | O Papel da variação do número de cópias genômicas no fenótipo clínico de deficiência intelectual em uma coorte retrospectiva da rede pública de saúde do Estado de Goiás | por |
| dc.title.alternative | The role of copy number variation in the clinical phenotype of intellectual disabilityin a retrospective cohort of public health network from Goiás State | eng |
| dc.type | Tese | por |