ABSTRACT
Introduction: Rare disorders that are genetically and clinically heterogeneous, such as mitochondrial diseases (MDs), have a challenging diagnosis. Nuclear genes codify most proteins involved in mitochondrial biogenesis, despite all mitochondria having their own DNA. The development of next-generation sequencing (NGS) technologies has revolutionized the understanding of many genes involved in the pathogenesis of MDs. In this new genetic era, using the NGS approach, we aimed to identify the genetic etiology for a suspected MD in a cohort of 450 Portuguese patients. Methods: We examined 450 patients using a combined NGS strategy, starting with the analysis of a targeted mitochondrial panel of 213 nuclear genes, and then proceeding to analyze the whole mitochondrial DNA. Results and Discussion: In this study, we identified disease-related variants in 134 (30%) analyzed patients, 88 with nuclear DNA (nDNA) and 46 with mitochondrial DNA (mtDNA) variants, most of them being pediatric patients (66%), of which 77% were identified in nDNA and 23% in mtDNA. The molecular analysis of this cohort revealed 72 already described pathogenic and 20 novel, probably pathogenic, variants, as well as 62 variants of unknown significance. For this cohort of patients with suspected MDs, the use of a customized gene panel provided a molecular diagnosis in a timely and cost-effective manner. Patients who cannot be diagnosed after this initial approach will be further selected for whole-exome sequencing. Conclusion: As a national laboratory for the study and research of MDs, we demonstrated the power of NGS to achieve a molecular etiology, expanding the mutational spectrum and proposing accurate genetic counseling in this group of heterogeneous diseases without therapeutic options.
ABSTRACT
Introduction: ?Eletronic tongue? is a device commonly used in the analysis of tastants, heavy metal ions, fruit juice, wines and also in the development of biosensors [1-3]. Briefly, the e-tongue is constituted by sensing units formed by ultrathin films of distinct materials deposited on gold interdigitated electrodes, which are immersed in liquid samples, followed by impedance spectroscopy measurements [1]. The e-tongue sensor is based on the global selectivity concept, i.e., the materials forming the sensing units are not selective to any substance in the samples, therefore, it allows the grouping of information into distinct patterns of response, enabling the distinction of complex liquid systems [1].Conclusion: Despite the differences of data obtained along distinct days of analysis, the e-tongue could detect differences among the samples tested, even considering the highly diluted cases studied.(AU)
