Two case reports of maturity-onset diabetes of the young type 3 caused by the hepatocyte nuclear factor 1α gene mutation

Abstract Maturity-onset diabetes of the young type 3 (MODY3) is a specific type of diabetes mellitus with inherited impairment of the islet β cell function due to the mutation in the hepatocyte nuclear factor 1α (HNF1α) gene. It is a rare condition and easily misdiagnosed as T1DM or T2DM. In this study, the clinical features of two unrelated Chinese MODY3 probands were described and analyzed. Next-generation sequencing was performed to identify the mutated genes, and Sanger sequencing was employed to verify the location of the pathogenic variant in the related family members. It was found that proband 1 inherited a start codon mutation c.2T>C (p.Met1?) in exon 1 of the HNF1α gene from his affected mother, and proband 2 inherited a frameshift mutation c.1136_1137del (p.Pro379fs) in exon 6 of the HNF1α gene also from her affected mother. Proband 1 and proband 2 differed in islet dysfunction, complications, and treatments due to their different disease durations and levels of hemoglobin A1c (HbA1c). The findings of this study demonstrate that early identification of MODY and diagnosis through genetic testing are critical for the treatment of the patient.