EP762 - ECE_3163 - Variant of uncertain significance in IRS 2 gene in patient with diabetes mellitus—case report
Abstract
A variant of uncertain significance (VUS) is a genetic variant identified during genetic testing but whose significance to clinical presentation is not known. Insulin receptor substrate 2 (IRS2) is important for pancreatic beta-cell survival and function, reduction of peripheral insulin sensitivity and insulin signaling.
A17 year old female patient was referred to endocrinologist because of high fasting blood glucose levels measuring up to 19 mmol/L. Her symptoms were present for two weeks and included fatigue, mouth dryness and polyuria. Prenatal and early childhood medical history were unremarkable. Her father was diagnosed with type 2 diabetes mellitus (T2DM) at the age of 40 years. Initial laboratory findings were: HbA1c 12.5%, C peptides 1.6 ng/ml. She was started with insulin therapy with oral antidiabetics (Metformin). After 3 months, HbA1c was 6.4%. She was positive for GAD (Glutamic Acid Decarboxylase) autoantibodies 26.3 U/ml, while ICA (Islet Cell Antibodies), IA-2 (Insulinoma-Associated Antigen 2) and ZnT8 (Zinc Transporter 8) autoantibodies were negative. After one year, HbA1c was 7.5% and C peptides levels were 2.6 ng/ml. Autoantibodies were negative. Since it is possible to find positive autoantibodies in 1% of MODY patients, MODY was suspected and clinical genome sequencing was requested. The result was undetermined, since one heterozygous VUS with a 67.5% probability of pathogenicity leading to diabetes mellitus was detected in the IRS2 gene. The genetic…
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