Therapeutic implications of novel mutations of the RFX6 gene associated with early-onset diabetes.

摘要: Identification of the genetic defect underlying early-onset diabetes is important for determining specific subtype, which would then permit appropriate treatment and accurate assessment recurrence risk in offspring. Given extensive clinical heterogeneity disease, high-throughput sequencing might provide additional diagnostic potential when Sanger ineffective. Our aim was to develop a targeted next-generation assay able detect mutations several genes involved glucose metabolism. All 13 known MODY genes, identified from genome-wide linkage study or association studies as increasing type 2 causing animal models, were included custom panel. We selected total 102 by performing targeting re-sequencing 30 patients negative GCK, HNF1α, HNF4α, HNF1β IPF1 at analysis. Previously unidentified variants RFX6 gene found three two them we also detected rare WFS1 ABCC8 genes. showed good therapeutic response dipeptidyl peptidase-4 (DPP4) inhibitors. reveals that provides highly sensitive method identification new causative diabetes. This approach may help understanding molecular etiology providing more personalized each subtype.