Meiotic instability of the pathogenic expansion (CAG)n=38 of the HTT gene in a familial case of Huntington´s disease.

Introduction: Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder, with progressive loss of striatal neurons, characterized by choreic movements, cognitive deterioration and psychiatric disturbances. HD is caused by the pathogenic expansion of the unstable trinucleotid...

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Detalles Bibliográficos
Autores: Barboza, Hazel Nunes, da Silva, Antônio Francisco Alves, Machado, Filipe Brum, Medina-Acosta, Enrique
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2010
País:Brasil
Institución:Faculdade de Medicina de Campos (FMC)
Repositorio:Revista Científica da Faculdade de Medicina de Campos
Idioma:portugués
OAI Identifier:oai:ojs.www.fmc.br:article/114
Acceso en línea:https://www.fmc.br/ojs/index.php/RCFMC/article/view/114
Access Level:acceso abierto
Palabra clave:análise de segregação,
distúrbio de repetição trinucleotídica
doença de Huntington
expansão de repetição trinucleotídica CAG
poliglutamina
teste genético
Genetic test
Huntington disease
polyglutamine
trinucleotide repeat disorder
trinucleotide repeat expansion CAG
segregation analysis
Descripción
Sumario:Introduction: Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder, with progressive loss of striatal neurons, characterized by choreic movements, cognitive deterioration and psychiatric disturbances. HD is caused by the pathogenic expansion of the unstable trinucleotide repeat (CAG)n in exon 1 of the huntingtin HTT gene. The symptoms generally manifest at late age (35-50years), and there is a significant inverse correlation between the threshold number of CAG repeats and the time of onset of symptoms.Objectives: To screen for alleles with expanded (CAG)n repeats in a nuclear family with clinical suspicion of HD, by meiotic segregation analysis, and to assist genetic counseling.Methods: Four adults (father, daughter 1, son and daughter 2) were included in the study, being father and son referred because of clinical findings suggestive of HD and the daughters asymptomatic.The (CAG)n alleles were determined by a specific quantitative fluorescent polymerase chain reaction assay.Results: Genotyping of (CAG)n alleles showed that the father, son and both daughters carried pathogenic alleles with 38, 45, 40 e 41 CAG repeats, respectively.Conclusion: Segregation analysis of (CAG)n alleles revealed paternal carrier transmission of the pathogenic unstable expansion (CAG)n=38 to the son and both daughters. Aiming at early and adequate genetic counseling in the daughters, the genetic test allowed identifying the pathogenic alleles in a rapid and precise manner.