Journal Article

Best practice guidelines for the molecular genetic diagnosis of maturity-onset diabetes of the young

Bellanné-Chantelot, C., Hattersley, A. T., Ellard, S.

2008

Overview

Aims/hypothesis Mutations in the GCK and HNF1A genes are the most common cause of the monogenic forms of diabetes known as ‘maturity-onset diabetes of the young’. GCK encodes the glucokinase enzyme, which acts as the pancreatic glucose sensor, and mutations result in stable, mild fasting hyperglycaemia. A progressive insulin secretory defect is seen in patients with mutations in the HNF1A and HNF4A genes encoding the transcription factors hepatocyte nuclear factor-1 alpha and -4 alpha. A molecular genetic diagnosis often changes management, since patients with GCK mutations rarely require pharmacological treatment and HNF1A/4A mutation carriers are sensitive to sulfonylureas. These monogenic forms of diabetes are often misdiagnosed as type 1 or 2 diabetes. Best practice guidelines for genetic testing were developed to guide testing and reporting of results. Methods A workshop was held to discuss clinical criteria for testing and the interpretation of molecular genetic test results. The participants included 22 clinicians and scientists from 13 countries. Draft best practice guidelines were formulated and edited using an online tool ( http://www.coventi.com ). Results An agreed set of clinical criteria were defined for the testing of babies, children and adults for GCK , HNF1A and HNF4A mutations. Reporting scenarios were discussed and consensus statements produced. Conclusions/interpretation Best practice guidelines have been established for monogenic forms of diabetes caused by mutations in the GCK , HNF1A and HNF4A genes. The guidelines include both diagnostic and predictive genetic tests and interpretation of the results.

• Publisher: Springer-Verlag,Springer Nature B.V
• Subject: Adolescent / Best practice / Child / Chromosome Mapping / Diabetes / Diabetes Mellitus, Type 2 / Diabetes Mellitus, Type 2 - diagnosis / Diabetes Mellitus, Type 2 - genetics / diagnosis / Genes / Genetic testing / Genetics / Glucose / Hepatocyte Nuclear Factor 1-alpha / Hepatocyte Nuclear Factor 1-alpha - genetics / Hepatocyte Nuclear Factor 4 / Hepatocyte Nuclear Factor 4 - genetics / Human Physiology / Humans / Hyperglycemia / Insulin / Internal Medicine / Medicine / Medicine & Public Health / Metabolic Diseases / Mutation / noninsulin-dependent diabetes mellitus / Polymorphism, Single Nucleotide / Practice Guidelines as Topic / Practice Guidelines as Topic - standards / Reproducibility of Results