Genetic Testing in Diabetes Mellitus

This chapter reviews genetic test for diabetes mellitus and provides guidelines for clinical diagnosis of monogenic forms of diabetes mellitus. Monogenic diabetes is stated to be a diverse group of disorders with different clinical presentation and genetic causes. Mutations in the same gene is mentioned to have dramatic effect on clinical presentation, with mutations in the insulin gene causing either mild hyperglycemia presenting later in life or as severe insulin deficiency presenting as permanent neonatal diabetes. Monogenic forms of diabetes may be familial, whereas in others it may be sporadic as a result of de novo mutation and this will be familial in subsequent generations. The genetic testing for diabetes involves sequencing the gene of interest including the promoter, protein coding regions, splice acceptor and donor sites, and sites of RNA processing. Besides sequencing, analyses to detect deletions of the gene or parts of the gene may be necessary. The different forms of monogenic diabetes are discussed with their clinical features, the specific gene to be tested and therapy. These monogenic forms include glucokinase related familial fasting hyperglycemia, transcription factors associated familial early-onset diabetes and transient and permanent neonatal diabetes.