Maturity-onset diabetes of the young (
MODY) is rare monogenic diabetes. However,
MODY is often undiagnosed or misdiagnosed. In this study, we aimed to investigate the pathogenic gene for diabetes and provide precise treatment for diabetes patients in three families. Three families with suspected
MODY were enrolled and screened for germline mutations using Whole exome sequencing (WES). Candidate pathogenic variants were validated in other family members and non-related healthy controls. Three heterozygous missense mutations in the ABCC8 gene (NM_001287174), c.1555 C>T (p.R519C), c.3706 A>G (p.I1236V), and c.2885 C>T (p.S962L) were found in families A, B, and C, respectively. All mutation sites cosegregated with diabetes, were predicted to be harmful by bioinformatics and were not found in non-related healthy controls. Two probands (onset ages, 8 and 12 years) were sensitive to
glimepiride. However, an insufficient dose (2 mg/day) led to
ketoacidosis. When the dosage of
glimepiride was increased to 4 mg/day,
blood sugar remained under control. A dose of 4 mg
glimepiride daily also effectively controlled
blood sugar in an adult patient 25-year-old. In addition, all patients were sensitive to
liraglutide, which could control
blood sugar better. These data suggest that ABCC8 was the pathogenic gene in three families with diabetes.
Glimepiride (2 mg/day) was not effective in controlling
blood sugar in children with ABCC8 mutations, however, 4 mg/daily
glimepiride was effective in both adults and children. Moreover,
liraglutide was effective in controlling
blood sugar in both adults and children with ABCC8 mutations.