Identification and Clinical Characteristics Analysis of HNF-1A Mutations p.I27L, p.S487N and p.G574S in Chinese Patients with MODY3

Abstract Background: Due to the rarity, the type 3 of maturity-onset diabetes of the young (MODY3) has not been explored comprehensively. The study aimed to describe and analyze the molecular and clinical characteristics of MODY3, which could help physicians understand the subtype of diabetes and increase the diagnosis rates in the future.Methods: Ten unrelated patients with suspected maturity-onset diabetes of the young (MODY) were included in the study based on information on family history and onset age. Sanger sequencing was used to identify cases with mutations in the hepatic nuclear factor 1A gene (HNF-1A). Results: Five patients were identified with MODY3, three cases (60%) with p.I27L mutation, one case (20%) with p.S487N mutation, and one case (20%) with p.G574S mutation. The average onset age was (23.00±3.00) years and the average age of diagnosis was (28.67±9.29) years. Most patients had typical clinical symptoms (polydipsia, polyuria, polyphagia, and weight loss). The main complications included diabetic ketoacidosis (DKA, 3/5,60%), diabetic macroangiopathy (2/5,40%), diabetic peripheral neuropathy (DPN,3/5,60%), diabetic nephropathy (DN,1/5,20%) and diabetic retinopathy (DR,1/5,20%). Four patients (80%) had fatty liver. The average body mass index (BMI) (26.39±4.67) kg/㎡, triglyceride (TG 2.95±1.43 mmol/L) and low-density lipoprotein (LDL-C 3.37±0.65 mmol/L) were beyond normal value. The glycosylated hemoglobin A1c (HbA1c 12.45±4.60 %), fasting plasma glucose (FPG 10.10±3.57 mmol/L) and postprandial plasma glucose (PPG 21.88±2.53 mmol/L) also increased dramatically. In addition, islet function examination revealed impaired secretion and slightly poor reserve function, which was similar to the changes inT2DM. All five patients used insulin, three (60%) also using antidiabetic drugs which did not include sulfonylureas.Conclusions: In brief, five patients were identified with MODY3. The mutation site could influence the onset age, the islet function and the incidence of complications. The age at diagnosis was 4.2 years later than the onset age. The control of diabetes was poor due to the inappropriate treatment. It is vital to make an early diagnosis and provide appropriate treatment for MODY3 patients.