Cytogenomic assessment of the diagnosis of 93 patients with developmental delay and multiple congenital abnormalities: The Brazilian experience

OBJECTIVE: The human genome contains several types of variations, such as copy number variations, that can generate specific clinical abnormalities. Different techniques are used to detect these changes, and obtaining an unequivocal diagnosis is important to understand the physiopathology of the diseases. The objective of this study was to assess the diagnostic capacity of multiplex ligation-dependent probe amplification and array techniques for etiologic diagnosis of syndromic patients. METHODS: We analyzed 93 patients with developmental delay and multiple congenital abnormalities using multiplex ligation-dependent probe amplifications and arrays. RESULTS: Multiplex ligation-dependent probe amplification using different kits revealed several changes in approximately 33.3% of patients. The use of arrays with different platforms showed an approximately 53.75% detection rate for at least one pathogenic change and a 46.25% detection rate for patients with benign changes. A concomitant assessment of the two techniques showed an approximately 97.8% rate of concordance, although the results were not the same in all cases. In contrast with the array results, the MLPA technique detected ∼70.6% of pathogenic changes. CONCLUSION: The obtained results corroborated data reported in the literature, but the overall detection rate was higher than the rates previously reported, due in part to the criteria used to select patients. Although arrays are the most efficient tool for diagnosis, they are not always suitable as a first-line diagnostic approach because of their high cost for large-scale use in developing countries. Thus, clinical and laboratory interactions with skilled technicians are required to target patients for the most effective and beneficial molecular diagnosis

Development of a software for storage and exploration of genomic data

A alta demanda por metodologias e técnicas para se analisar e armazenar os dados genômicos, que crescem tanto em quantidade quanto em complexidade a cada nova geração, provocou uma explosão de softwares de análises e bancos de dados disponíveis comercialmente. Entretanto a discrepância entre as metodologias empregadas, entre um programa e a eventual necessidade de se usar mais de um software para realizar a análise dos dados genômicos obtidos no laboratório, acaba dificultando o trabalho do analista-técnico, principalmente se ele não tiver conhecimentos prévios em informática ou bioinformática. Os diferentes valores de mercados e diferentes outputs (resultado final liberado pelo software) agregam dificuldade ao problema. Propusemos nesse trabalho a criação de um software acessível capaz de permitir uma maior flexibilidade para o analista gerenciar seus dados, seja para armazená-los no banco de dados ou para explorá-los de forma direcionada. Dessa forma, desenvolvemos um programa para armazenar e explorar da melhor forma os dados genômicos obtidos pelas atividades do Laboratório de Citogenômica. O sistema oferece segurança, uma interface gráfica de utilizador simples e funcional garantindo que o analista-técnico gerencie seus dados de forma rápida e segura. Facilitando a organização e a compreensão de todo o volume de dados genômicos cientificamente relevantes obtidos nos laboratórios que aplicam novas tecnologias para análise do DNAThe high demand for methodologies and techniques to analyze and store genomic data, which grows both in quantity and complexity with each new generation, has caused an explosion of commercially available analysis software and databases. However, the discrepancy between the methodologies used, between a program and the possible need to use more than one software to perform the analysis of the genomic data obtained in the laboratory, ends up hindering the work of the technical analyst, especially if he does not have previous knowledge in informatics or bioinformatics. The different market values and different outputs (final result released by the software) add difficulty to the problem. The creation of software capable of allowing greater flexibility for the analyst to manage his data, either to store it in the proposed local database or to explore it in a targeted manner. Thus, we have developed a program to store and explore in the best way the genomic data obtained by the activities of the Laboratório de Citogenômica. The system offers security, a simple and functional graphical user interface ensuring that the analyst-technician manages his data quickly and safely. Facilitating the organization and understanding of the entire volume of scientifically relevant genomic data obtained in laboratories that apply new technologies for DNA analysi

Cytogenomic assessment of the diagnosis of 93 patients with developmental delay and multiple congenital abnormalities: The Brazilian experience

OBJECTIVE: The human genome contains several types of variations, such as copy number variations, that can generate specific clinical abnormalities. Different techniques are used to detect these changes, and obtaining an unequivocal diagnosis is important to understand the physiopathology of the diseases. The objective of this study was to assess the diagnostic capacity of multiplex ligation-dependent probe amplification and array techniques for etiologic diagnosis of syndromic patients. METHODS: We analyzed 93 patients with developmental delay and multiple congenital abnormalities using multiplex ligation-dependent probe amplifications and arrays. RESULTS: Multiplex ligation-dependent probe amplification using different kits revealed several changes in approximately 33.3% of patients. The use of arrays with different platforms showed an approximately 53.75% detection rate for at least one pathogenic change and a 46.25% detection rate for patients with benign changes. A concomitant assessment of the two techniques showed an approximately 97.8% rate of concordance, although the results were not the same in all cases. In contrast with the array results, the MLPA technique detected ∼70.6% of pathogenic changes. CONCLUSION: The obtained results corroborated data reported in the literature, but the overall detection rate was higher than the rates previously reported, due in part to the criteria used to select patients. Although arrays are the most efficient tool for diagnosis, they are not always suitable as a first-line diagnostic approach because of their high cost for large-scale use in developing countries. Thus, clinical and laboratory interactions with skilled technicians are required to target patients for the most effective and beneficial molecular diagnosis