New type of diabetes caused by a genetic mutation

New type of diabetes caused by a genetic mutation


Scientists have identified a new type of diabetes caused by a mutation in the gene RFX6.

Authors sequenced  maturity-onset diabetes of the young (MODY) cases with unknown aetiology and compared variant frequencies to large public databases. From 36 European patients, they identified two probands with novel RFX6 heterozygous nonsense variants. RFX6 protein truncating variants are enriched in the MODY discovery cohort compared to the European control population.

Researchers find similar results in non-Finnish European  and replication cohorts. RFX6 heterozygotes have reduced penetrance of diabetes compared to common HNF1A and HNF4A-MODY mutations (27, 70 and 55% at 25 years of age, respectively). 

Individuals carrying the RFX6 mutation have a high probability of developing diabetes: it can start early, before the age of 20 years, and by the age of 50 years 80% has developed the disease. It is transmitted from parents to children and may affect many generations in the same family.

RFX6 diabetes often requires insulin treatment because patients have reduced insulin secretion by the pancreas.

Researchers identified in these patients a reduced production of the hormone GIP that stimulates insulin secretion. The hormone GIP is produced by the intestine after eating and is an important regulator of insulin secretion. RFX6 diabetes is the first type of diabetes discovered to be related to low GIP production.

The identification of this novel disease mechanism suggests that GIP analogs (i.e. drugs with a structure similar to GIP) may provide a novel treatment option for patients with RFX6 diabetes. These new observations published in the journal Nature Communications emphasize the need to identify specific forms of diabetes in order to provide personalized therapy to patients.