title: Monogenic models: what have the single gene disorders taught us?
abstract: Monogenic diabetes constitutes a heterogeneous group of single gene disorders. The molecular background and clinical picture of many of these diseases have been described. While each of these forms is much less prevalent than multifactorial type 1 and type 2 diabetes mellitus (T2DM), together they affect millions of patients worldwide. Genetic diagnosis, which has become widely available, is of great clinical importance for patients with single gene diabetes. It helps to fully understand the pathophysiology of the disease, tailor the optimal hypoglycemic treatment, and define the prognosis for the entire family. Monogenic diabetes forms can be divided into 2 large groups, resulting from impaired insulin secretion or from an abnormal response to insulin. There are several lessons we have been taught by single-gene diabetes. We learned that the gene responsible for the occurrence of diabetes can be identified if an appropriate search strategy is used. In addition, discoveries of genes responsible for monogenic disorders pointed to them as susceptibility candidates for T2DM. Moreover, establishing that some families of proteins or biological pathways, such as transcription factors or potassium channel subunits, are involved in monogenic diabetes sparked research on their involvement in multifactorial diabetes. Finally, the example of single gene diabetes, particularly HNF1A MODY and permanent neonatal diabetes associated with the KCNJ11 and ABCC8 genes, all efficiently controlled on sulfonylurea, inspires us to continue the efforts to tailor individual treatment for T2DM patients. In this review paper, we summarize the impact of single gene disease discoveries on diabetes research and clinical practice.
authors.affiliation: Department of Metabolic Diseases, Jagiellonian University, Medical College, 15 Kopernika Street, 31-501, Krakow, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Klupa
authors.forename: Jan
authors.initials: J
authors.lastname: Skupien
authors.forename: Maciej T
authors.initials: MT
authors.lastname: Malecki
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005838:Genotype; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics*; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008297:Male; D008954:Models, Biological; D009154:Mutation; D010597:Pharmacogenetics; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D011955:Receptors, Drug / Q000235:genetics*; D013453:Sulfonylurea Compounds / Q000627:therapeutic use; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel
chemical_list: D018528:ATP-Binding Cassette Transporters; D051538:Hepatocyte Nuclear Factor 1-alpha; D007004:Hypoglycemic Agents; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D013453:Sulfonylurea Compounds; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel; C496487:HNF1A protein, human