Alterações genômicas e transtornos neuropsiquiátricos em familiares de autistas
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Data
2019-02-25
Autores
Rosan, Dante Bruno Avanso [UNESP]
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Universidade Estadual Paulista (Unesp)
Resumo
O Transtorno do Espectro Autista (TEA), ou Autismo, corresponde a um grupo de afecções neuropsiquiátricas complexas, de etiologia heterogênea e desconhecida na maioria dos casos. A prevalência é muito alta na população em geral e os afetados são caracterizados por dificuldade de comunicação e socialização, além de manias e repetições. Familiares de autistas apresentam frequências significativamente maiores de alterações comportamentais vinculadas às características autísticas e este fenótipo mais amplo é conhecido como Broad Autism Phenotype (BAP). Há centenas de genes candidatos ao autismo ou regiões genômicas que apresentam alterações, que estão descritas não apenas em casuísticas de autistas, mas também de indivíduos com outros transtornos do comportamento, o que evidencia uma sobreposição etiológica entre tais afecções. Além disso, em uma mesma família, uma alteração genética pode estar presente em parentes assintomáticos, naqueles com BAP e naqueles com outros transtornos neuropsiquiátricos. Os estudos em familiares se limitam frequentemente à investigação de pais e irmãos. Este projeto objetivou investigar a presença de alterações genéticas previamente detectadas em autista,s em seus pais, irmãos e em outros familiares com transtornos neuropsiquiátricos, além da presença do BAP e de outros transtornos neuropsiquiátricos nas genealogias dos autistas. A presença e os aspectos relacionados ao BAP em pais de autistas também foram estudados e comparados com um grupo composto de pais de indivíduos com deficiência intelectual idiopática, sem autismo, e com um grupo de pais de indivíduos sem queixas de transtornos neurocomportamentais. As alterações moleculares previamente detectadas em indivíduos com TEA foram investigadas em seus familiares com a utilização de diferentes metodologias já implantadas nos laboratórios participantes deste estudo. O BAP foi investigado com a utilização do BAPQ (Broad Autism Phenotype Questionnaire), por meio de entrevistas previamente agendadas. 18 (36%) familiares de autistas apresentaram a mesma alteração genética encontrada no caso índice, sendo que oito (50%) deles também tinham BAP positivo. BAP foi observado nos três grupos de pais investigados, com frequência significativamente maior nos pais de autistas, que também apresentaram maiores escores para personalidade rígida do que os pais dos outros grupos. Nossos achados estão de acordo com os da literatura e acrescentam que algumas alterações genômicas podem predispor não apenas ao autismo como à esquizofrenia, transtorno do déficit de atenção com hiperatividade (TDAH) e BAP, além do fato de que BAP também é observado em pais de indivíduos com deficiência intelectual. É importante avaliar a presença de BAP em pais de autistas e de outros indivíduos com afecções do neurodesenvolvimento, como a deficiência intelectual, pois os resultados podem direcionar a orientação de riscos e o Aconselhamento Genético das famílias.
Autism Spectrum Disorder (ASD), or Autism, is a group of complex neuropsychiatric disorders, witch heterogeneous and unknown etiology in most cases. The prevalence is high in the population and those affected are characterized by impairments in communication and socialization, as well restricted stereotypes. Relatives of individuals with autism have significantly higher frequencies of behavioral alterations related to autistic characteristics and this is known as Broad Autism Phenotype (BAP). There are hundreds of autism candidate genes or genomic regions that present variations, which are described not only in autistic cases, but also in individuals with other behavioral disorders, which shows an etiological overlap between these conditions. In addition, in a single family, a genetic alteration may be present in asymptomatic relatives, in those with BAP and in those with other neuropsychiatric disorders. Studies in relatives are often limited to the investigation of parents and siblings. This project aimed to investigate the presence of genetic alterations previously detected in autistic individuals, in their parents, siblings and other relatives with neuropsychiatric disorders, besides the presence of BAP and other neuropsychiatric disorders in the autistic genealogy. The presence of BAP parents of autistic children and the aspects related to this phenotype were also studied and compared to a group of parents of individuals with idiopathic intellectual disability without autism and with a group of parents of individuals without complaints of neurobehavioral disorders. The molecular alterations previously detected in individuals with ASD were investigated in their relatives with the use of different methodologies already implanted in the laboratories participating in this study. The BAP was investigated using the BAPQ (Broad Autism Phenotype Questionnaire), through interviews previously scheduled. 18 (36%) relatives presented the same genetic alteration that had been found in the non-autistic relative, with eight of them (50%) also having BAP positive. BAP was observed in the three groups of parents investigated, with a significantly higher frequency in the parents of autistic individuals, who also presented higher scores for rigid personality than the parents of the other groups. Our findings are in agreement with the literature, and add that some genomic alterations may predispose not only to autism but also to schizophrenia, Attention Deficit Hyperactivity Disorder" (ADHD) and BAP, which is also seen in parents of individuals with intellectual disability. It is important to evaluate the presence of BAP in parents of autistic individuals and other individuals with neurodevelopmental conditions, such as intellectual disability, because the results can guide the risk orientation and the Genetic Counseling of families.
Autism Spectrum Disorder (ASD), or Autism, is a group of complex neuropsychiatric disorders, witch heterogeneous and unknown etiology in most cases. The prevalence is high in the population and those affected are characterized by impairments in communication and socialization, as well restricted stereotypes. Relatives of individuals with autism have significantly higher frequencies of behavioral alterations related to autistic characteristics and this is known as Broad Autism Phenotype (BAP). There are hundreds of autism candidate genes or genomic regions that present variations, which are described not only in autistic cases, but also in individuals with other behavioral disorders, which shows an etiological overlap between these conditions. In addition, in a single family, a genetic alteration may be present in asymptomatic relatives, in those with BAP and in those with other neuropsychiatric disorders. Studies in relatives are often limited to the investigation of parents and siblings. This project aimed to investigate the presence of genetic alterations previously detected in autistic individuals, in their parents, siblings and other relatives with neuropsychiatric disorders, besides the presence of BAP and other neuropsychiatric disorders in the autistic genealogy. The presence of BAP parents of autistic children and the aspects related to this phenotype were also studied and compared to a group of parents of individuals with idiopathic intellectual disability without autism and with a group of parents of individuals without complaints of neurobehavioral disorders. The molecular alterations previously detected in individuals with ASD were investigated in their relatives with the use of different methodologies already implanted in the laboratories participating in this study. The BAP was investigated using the BAPQ (Broad Autism Phenotype Questionnaire), through interviews previously scheduled. 18 (36%) relatives presented the same genetic alteration that had been found in the non-autistic relative, with eight of them (50%) also having BAP positive. BAP was observed in the three groups of parents investigated, with a significantly higher frequency in the parents of autistic individuals, who also presented higher scores for rigid personality than the parents of the other groups. Our findings are in agreement with the literature, and add that some genomic alterations may predispose not only to autism but also to schizophrenia, Attention Deficit Hyperactivity Disorder" (ADHD) and BAP, which is also seen in parents of individuals with intellectual disability. It is important to evaluate the presence of BAP in parents of autistic individuals and other individuals with neurodevelopmental conditions, such as intellectual disability, because the results can guide the risk orientation and the Genetic Counseling of families.
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Palavras-chave
Transtorno do Espectro do Autismo, transtornos mentais, mutações, CNVs, Autism Spectrum Disorder, Broad Autism Phenotype, variations