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Las talasemias son desórdenes autosómicos recesivos de las cadenas de hemoglobina que poseen expresión clínica variable según el tipo de mutación o deleción. Presentamos el caso de dos jóvenes mujeres costarricenses no relacionadas entre sí y ambas diagnosticadas con la mutación común en el codón 39 (C>T) (β0) en combinación con la deleción siciliana (δβ0) 13.4 kb. La caracterización de doble heterocigota no había sido descrita antes en la literatura médica, y discutimos el significado de este genotipo que causa un defecto tipo β0 talasemia transfusión dependiente.

Background Next generation sequencing (NGS) technologies have improved the study of hereditary diseases. Since the evaluation of bioinformatics pipelines is not straightforward, NGS demands effective strategies to analyze data that is of paramount relevance for decision making under a clinical scenario. According to the benchmarking framework of the Global Alliance for Genomics and Health (GA4GH), we implemented a new simple and user-friendly set-theory based method to assess variant callers using a gold standard variant set and high confidence regions. As model, we used TruSight Cardio kit sequencing data of the reference genome NA12878. This targeted sequencing kit is used to identify variants in key genes related to Inherited Cardiac Conditions (ICCs), a group of cardiovascular diseases with high rates of morbidity and mortality. Results We implemented and compared three variant calling pipelines (Isaac, Freebayes, and VarScan). Performance metrics using our set-theory approach showed high-resolution pipelines and revealed: (1) a perfect recall of 1.000 for all three pipelines, (2) very high precision values, i.e. 0.987 for Freebayes, 0.928 for VarScan, and 1.000 for Isaac, when compared with the reference material, and (3) a ROC curve analysis with AUC > 0.94 for all cases. Moreover, significant differences were obtained between the three pipelines. In general, results indicate that the three pipelines were able to recognize the expected variants in the gold standard data set. Conclusions Our set-theory approach to calculate metrics was able to identify the expected ICCs related variants by the three selected pipelines, but results were completely dependent on the algorithms. We emphasize the importance to assess pipelines using gold standard materials to achieve the most reliable results for clinical application.

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