A case of monogenic diabetes mellitus caused by a novel heterozygous RFX6 nonsense mutation in a 14-year-old girl

Monogenic diabetes mellitus (DM) is a single gene disorder, primarily characterized by impairment in the development or function of pancreatic beta cells.A 14-year-old girl was initially diagnosed with type 2 DM. The patient did not have any anti-islet autoantibody and showed acanthosis nigricans. She was managed with long-acting insulin and oral hypoglycemic agent, but HbA1c was still 9.3% after 1 year of management. Her mother already had type 2 DM at 46-year-old and was on medication. Under the possibility of familial monogenic DM, targeted exome sequencing was performed which included 29 genes associated with monogenic DM. Nonsense mutation of the gene RFX6 (c.2661T>A, p.Tyr887∗) was found. After adding Glucagon-like peptide-1 (GLP-1) receptor agonist, HbA1c improved from 8.8 to 6.8% and body mass index (BMI) also improved from 31.0 to 29.2 kg/m2.It may be worth investigating genetic etiology in early-onset autoantibody-negative DM for specific genetic diagnosis and better management.