Next-generation sequencing in Brazilian MODY patients: a pilot study
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KeywordsBeta Cell Sanger Sequencing Pilot Project Good Glycemic Control Typical Clinical Feature
Maturity-Onset Diabetes of the Young (MODY) is the most common form of monogenic diabetes. Genetic analysis is required to confirm the diagnosis. Conventional genetic testing uses Sanger sequencing. Currently, Next-generation sequencing (NGS) has proven to be cost-effective. To date, there is no NGS study for MODY in Brazil.
To validate a new assay for molecular diagnosis of MODY using targeted-NGS.
Materials and methods
We have completed a pilot project including 7 unrelated subjects with MODY phenotype. Genetic sequencing was performed using Illumina NGS platform (MiSeq), allowing analysis of 13 MODY genes simultaneously. All exonic and intronic regions of these genes were evaluated. Two cases were not tested before. In other 5 cases, a previous analysis using Sanger sequencing of GCK and HNF1A genes had been done. Three subjects had already a genetic diagnosis of MODY by Sanger method and were selected to validate NGS Results. And the other 2 cases had typical clinical features but negative Sanger analysis.
In our pilot project, targeted-NGS was able to confirm MODY diagnosis in all cases submitted to Sanger sequencing (3 positive controls and 2 previously negative cases). In other two not tested before, this new method could identify the pathogenic variants. Thus, NGS can be considered an effective tool for diagnosing clinical suspicious cases of MODY, appearing to be a promising technique.
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