Clinical relevance of copy number variations detected by array-coh in six patients with unexplained non-syndromic intellectual disability

Detalhes bibliográficos
Autor(a) principal: Ferraz, Ana Isabel Borges
Data de Publicação: 2012
Tipo de documento: Dissertação
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10316/36377
Resumo: Trabalho final de mestrado integrado em Medicina, área de Pediatria, apresentado á Faculdade de Medicina da Universidade de Coimbra
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spelling Clinical relevance of copy number variations detected by array-coh in six patients with unexplained non-syndromic intellectual disabilityGénotipoFénotipoDeficiência intelectualDomínio/Área Científica::Ciências MédicasTrabalho final de mestrado integrado em Medicina, área de Pediatria, apresentado á Faculdade de Medicina da Universidade de CoimbraIntellectual disability (ID) represents a health problem of great relevance for the public health services and for the families and is one of the most common neurodevelopmental disorders, affecting 1 to 3% of children. Epidemiological studies show that genetic mutations contribute in about 15% to the etiology in milder forms. When ID is present with other symptoms or physical features, the identification of the causative effect is not so difficult to educe. On the contrary, ID can be present as a sole clinical feature or with additionally subtle symptoms, sometimes difficult to diagnose. In about half the cases of ID, despite a thorough medical history and laboratory investigation widened, the etiology remains unknown. In recent years, submicroscopic structural variations in copy number, known as copy number variations (CNVs) of a specific chromosomal region, have been implicated in the etiology of ID. Novel high resolution, whole genome technologies, such as array-based comparative genomic hybridization (array- CGH), improve the detection rate of submicroscopic chromosomal aberrations, allowing the re-investigation of cases where conventional cytogenetics failed to detect any mutation. However, the application of this contemporary molecular technology has also resulted in the discovery of widespread CNVs in human genome and understanding the clinical significance of these alterations on phenotype variation has been a real challenge, especially in non-syndromic ID (NS-ID). Although it has already contributed to the etiological classification of a large portion of ID patients, sometimes it can be difficult to pinpoint for certain that the alterations found are the cause of the phenotype, especially in NS-ID cases. With the rapid discovery of the genetic causes underlying NS-ID and the pathways and processes involved in neurodevelopment and cognition, this will inevitably feedback into clinical diagnostics of these forms of ID. The aim of this study is to use array-CGH for the screening of patients with “idiopathic” ID, in order to detect submicroscopic copy number changes and correlate them with the phenotype. In this study, a sample of 42 children monitored at the Neurodevelopmental and Autistic Unit of the Carmona da Mota Pediatric Hospital of Coimbra, with the diagnosis of non-syndromic ID (NS-ID) or with minor dysmorphisms based on clinical observation and implementation of gold standard scales for ID diagnosis, are being analyzed by array-CGH (17 Mb resolution level) in Life and Health Sciences Research Institute (ICVS) from Minho´s University. According to available laboratorial results, we selected six patients from the sample of 42 to analyze whether the high resolution, genomewide, microarray-based, copy number screening would allow the identification of small rearrangements not detected by other techniques which could be the explanation for their NS-ID or learning disorders. In these six patients, we found two likely pathogenic chromosomal alterations, the duplications in Xp11.22 and 2q11.2 chromosomes. Based on current evidence, other potential pathogenic alterations were found and in many others it was not possible to assess their clinical significance. During the interpretation of the clinical relevance of CNVs, many generalizations are made, as regards to the type of the event, size, gene content and inheritance. Sometimes this can lead to the exclusion of CNVs that could have a real impact on the phenotype. Current evidence shows that small duplications can have a role in the phenotype and even alterations that do not encompass any genes may affect the genetic expression. Moreover, environmental factors may also have an impact on the way genotype is expressed. This study underlines the importance of a new integrated and multidimensional model for the interpretation of alterations found by array-CGH, specially in cases of NS-ID.2012-03info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesishttp://hdl.handle.net/10316/36377http://hdl.handle.net/10316/36377engFerraz, Ana Isabel Borgesinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2022-01-20T17:48:43Zoai:estudogeral.uc.pt:10316/36377Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:44:03.779641Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Clinical relevance of copy number variations detected by array-coh in six patients with unexplained non-syndromic intellectual disability
title Clinical relevance of copy number variations detected by array-coh in six patients with unexplained non-syndromic intellectual disability
spellingShingle Clinical relevance of copy number variations detected by array-coh in six patients with unexplained non-syndromic intellectual disability
Ferraz, Ana Isabel Borges
Génotipo
Fénotipo
Deficiência intelectual
Domínio/Área Científica::Ciências Médicas
title_short Clinical relevance of copy number variations detected by array-coh in six patients with unexplained non-syndromic intellectual disability
title_full Clinical relevance of copy number variations detected by array-coh in six patients with unexplained non-syndromic intellectual disability
title_fullStr Clinical relevance of copy number variations detected by array-coh in six patients with unexplained non-syndromic intellectual disability
title_full_unstemmed Clinical relevance of copy number variations detected by array-coh in six patients with unexplained non-syndromic intellectual disability
title_sort Clinical relevance of copy number variations detected by array-coh in six patients with unexplained non-syndromic intellectual disability
author Ferraz, Ana Isabel Borges
author_facet Ferraz, Ana Isabel Borges
author_role author
dc.contributor.author.fl_str_mv Ferraz, Ana Isabel Borges
dc.subject.por.fl_str_mv Génotipo
Fénotipo
Deficiência intelectual
Domínio/Área Científica::Ciências Médicas
topic Génotipo
Fénotipo
Deficiência intelectual
Domínio/Área Científica::Ciências Médicas
description Trabalho final de mestrado integrado em Medicina, área de Pediatria, apresentado á Faculdade de Medicina da Universidade de Coimbra
publishDate 2012
dc.date.none.fl_str_mv 2012-03
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10316/36377
http://hdl.handle.net/10316/36377
url http://hdl.handle.net/10316/36377
dc.language.iso.fl_str_mv eng
language eng
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instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
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