A novel ABCC8 mutation illustrates the variability of the diabetes phenotypes associated with a single mutation.

AIM: ATP-sensitive potassium channels are important regulators of insulin secretion. They consist of four sulphonylurea receptor (encoded by ABCC8) and four inwardly rectifying protein (encoded by KCNJ11) subunits. Activating ABCC8 mutations lead to decreased insulin secretion and to diabetes. Wide phenotype variability is associated with single ABCC8 mutations, ranging from transient or permanent neonatal diabetes (ND) with or without developmental delay (DEND syndrome) to very mild phenotypes. This report describes the case of a Caucasian infant diagnosed with ND at the age of 2 months due to a novel ABCC8 missense mutation.

METHODS: ABCC8 was analyzed by sequence analysis. The mutation was present in the patient and her family and was found to be associated with phenotypes ranging from ND to asymptomatic impaired fasting glucose (IFG).

RESULTS: A novel His863Tyr ABCC8 mutation was identified in a 2-month-old girl diagnosed with ND. After an initial insulin treatment, treatment with glibenclamide was initiated and the treatment with insulin discontinued. The same mutation was found in her father, who had been fortuitously diagnosed with diabetes and had an HbA(1c) level of 9% (74.8 mmol/mol). The patient's brother and mother both had normal fasting glucose, and were not found to be carriers of the mutation. However, the same mutation was found in her grandmother, who had been asymptomatic and discovered IFG (6.9 mmol/L) with an HbA(1c) of 6.8% (50.8 mmol/mol).

CONCLUSION: This case describes a novel ABCC8 mutation and offers a further illustration of the highly variable phenotypes associated with an identical mutation present across three generations.