Genomic screening for monogenic forms of diabetes

Adult-onset, or type II diabetes mellitus (T2DM) has a complex genetic architecture, from hundreds of genes with low penetrance, common susceptibility variants (e.g., TCF7L2), to a set of more than ten genes that, when mutated, can cause a single-gene or Mendelian form of T2DM (e.g., GCK). It is a clinical challenge to identify patients with the uncommon (2–3%) form of T2DM, typically classified as maturity-onset diabetes of the young (MODY). Bansal et al. (BMC Med 15:213, 2017) used a gene panel test approach to test patients with diabetes for single-gene causes of MODY. They found that nearly 2% of younger patients had pathogenic variants in one of seven genes. These data confirm prior studies showing that Mendelian or single-gene MODY can masquerade as garden variety T2DM. The implications of these results for wider general medicine and the future implementation of clinical genome sequencing are discussed. Please see related article: https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-017-0977-3