title: Diagnosis of monogenic diabetes: 10-Year experience in a large multi-ethnic diabetes center.
abstract: OBJECTIVE
  Monogenic 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.
  
  
  METHODS
  We 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.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  Existing 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.
authors.affiliation: Guy's and St Thomas' NHS Foundation Trust London UK.
authors.forename: Ellen Ra
authors.initials: ER
authors.lastname: Thomas
authors.affiliation: Guy's and St Thomas' NHS Foundation Trust London UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Brackenridge
authors.affiliation: Guy's and St Thomas' NHS Foundation Trust London UK.
authors.forename: Julia
authors.initials: J
authors.lastname: Kidd
authors.affiliation: Guy's and St Thomas' NHS Foundation Trust London UK.
authors.forename: Dulmini
authors.initials: D
authors.lastname: Kariyawasam
authors.affiliation: Guy's and St Thomas' NHS Foundation Trust London UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Carroll
authors.affiliation: Royal Devon and Exeter Hospital Exeter UK.
authors.forename: Kevin
authors.initials: K
authors.lastname: Colclough
authors.affiliation: Royal Devon and Exeter Hospital Exeter UK.
authors.forename: Sian
authors.initials: S
authors.lastname: Ellard
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D003920:Diabetes Mellitus / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques; D009154:Mutation; D055815:Young Adult
keywords: Diabetes mellitus; Genetic testing; Hepatocyte nuclear factor 1‐alpha