HNF1A gene mutation (c.811del, p.Arg271Glyfs) causing maturity onset of diabetes of the young 3: a case study of an Indian patient

Background: Maturity-Onset Diabetes of the Young (MODY) is a rare type of diabetes which starts in early adulthood and its prevalence is less than 5%. This can be an underestimate as it is usually misdiagnosed either as Type 1 or Type 2 diabetes. MODY can be classified to different types and determining its type through genetic testing would be the best recommendation for the management of disease. In this report, a case study is presented to determine the genetic cause of diabetes, suspected to be MODY. Case history: The presented case was diagnosed with diabetes at the age of 17 with a strong family history of diabetes. The individual was on insulin (12 units) with high random blood sugar levels (200 to 300 mg/dL) and HbA1c (9.2%, 77 mmol/mol). Whole exome sequencing has shown presence of a known likely pathogenic variant in HNF1A gene (chr12: 121432062, c.811del, p.Arg271Glyfs), known to cause MODY3. Other unaffected family members were screened for the variant using Sanger sequencing, but the results were negative. The association of this variant with the disease is reported for the first time in Indian population. Conclusion: Determination of genetic cause of diabetes is important for accurate diagnosis and prognosis. With appropriate treatment, such as sulphonylurea therapy, blood sugars can be brought under control and over time painful insulin therapy could be discontinued. This case clearly indicates importance of genetic screening to treat and manage diabetes in a right way.