Phenotypic heterogeneity and polygenic risk scores in a family of maturity-onset diabetes of the young

Diagnosis of a diabetes subtype leads to more precise management and informs the likelihood of diabetes in other family members. Patients with hepatocyte nuclear factor-1 alpha (<i>HNF1A</i>)-maturity-onset diabetes of the young (MODY) are highly sensitive to sulfonylureas, and a correct diagnosis can lead to more appropriate treatment. A patient may carry multiple genetic variants that contribute to the heterogeneity of phenotypes, trajectories, and outcomes. Polygenic risk score (PRS) is a useful tool to estimate an individual's genetic susceptibility to polygenic type 2 diabetes (T2D). Combining monogenic diabetes testing with PRS may explain the heterogeneity of phenotypes and clinical course among family members of patients with MODY. Herein, we report a nonobese Thai man with <i>HNF1A</i>-MODY due to a partial gene deletion. This has led to the same diagnosis in other family members diagnosed with T2D with heterogeneous presentations due to variable PRS and clinical risk factors.