Abstract
Aims/IntroductionMonogenic diabetes accounts for approximately 1–2% of all diabetes, and is difficult to distinguish from type 1 and type 2 diabetes. Molecular diagnosis is important, as the molecular subtype directs appropriate treatment. Patients are selected for testing according to clinical criteria, but up to 80% of monogenic diabetes in the UK has not been correctly diagnosed. We investigated outcomes of genetic testing in our center to compare methods of selecting patients, and consider avenues to increase diagnostic efficiency.Materials and MethodsWe reviewed 36 probands tested for monogenic diabetes in the last 10 years in a large adult diabetes outpatient clinic, serving an ethnically diverse urban population. We compared published clinical criteria and an online maturity onset diabetes of the young calculator applied to these 36 patients, and presented the predictions together with the molecular results.ResultsThe overall mutation detection rate was 42%, reflecting the strict clinical selection process applied before genetic testing. Both methods had high sensitivity for identifying patients with mutations: 88 and 89% for the clinical criteria and online calculator, respectively. Cascade testing in a total of 16 relatives led to diagnosis of a further 13 cases.ConclusionsExisting patient selection criteria were effective in identifying patients with monogenic forms of diabetes, but the number of patients missed using these strict criteria is unknown. Because of the potential savings resulting from correct molecular diagnosis, it is possible that testing a larger pool of patients using less stringent selection criteria would be cost‐effective. Further evidence is required to inform this assessment.
Highlights
It is known that 1–2% of patients with diabetes have a monogenic cause of their disease, which can result from mutations in a number of different genes
36 probands were seen in the adult diabetes clinic, and were tested for one or more of the monogenic diabetes genes GCK, HNF1A, HNF4A and HNF1B or the mitochondrial m.3243A>G mutation
The focus of this study was genetic testing patterns and outcomes within the adult diabetes center, and the remainder of this report focuses on the 36 probands tested in the adult diabetes clinic
Summary
It is known that 1–2% of patients with diabetes have a monogenic cause of their disease, which can result from mutations in a number of different genes. HNF1A and HNF4A mutations cause autosomal dominant diabetes, which usually occurs in childhood or early adulthood, and is responsive to treatment with sulphonylureas[1]. Mutations in the GCK gene cause autosomal dominant lifelong stable fasting hyperglycemia, which does not require treatment, as patients do not appear to develop the complications of diabetes[2]. Clinical criteria for selecting patients for molecular testing have been produced, but these are detailed and complex because of the heterogeneous nature of monogenic forms of diabetes, and the mutation detection rate when
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