1658-P: A Novel Mutation in Hepatocyte Nuclear Factor-1 Beta (HNF1B) in Maturity-Onset Diabetes of the Young 5 (MODY5)

Abstract

Maturity-onset diabetes of the young (MODY) is a group of dominantly inherited non-autoimmune diabetes characterized by early onset. Delayed diagnosis or misdiagnosis as type 1 or 2 diabetes is common, but early and correct diagnosis of MODY is important because it significantly alters the management of both the patient and his or her relatives. MODY5 is caused by mutations in the HNF1B, associated with renal and pancreatic abnormalities. Recently, we had identified a novel pathogenic mutation in IVS3-1G>C of HNF1B, in a Japanese MODY family. A 30-year-old male presented to our office with a diagnosis of NIDDM at age 15; autoimmune antibodies were negative, glycemia was initially managed with basal-bolus insulin. Abdominal ultrasound showed bilateral hyperechogenic kidneys but unlike with the reported typical abnormalities in MODY5, only a few renal cysts were observed, and pancreas was intact. An initial diagnosis of early-onset type 2 diabetes was made. However, the case subsequently showed high probability of MODY, when he reported a strong family history of early-onset diabetes in his sister, his father and paternal grandmother. Genetic testing performed in him, his sister and his father revealed shared unreported gene mutation g.37731831C>G (GRCH38 Chr17) in the HNF1B gene suggesting a diagnosis of MODY5. The mutation locates in the splicing site which may result in the production of abnormal proteins or failure of protein synthesis. Our MODY5 case was unique in the point that despite the mild renal morphological abnormalities, the proband had renal dysfunction and microalbuminuria from the early stage of disease, evoking the importance of considering the possibility of monogenic diabetes even in scarce structural abnormalities but having atypical diabetes with strong family history. It also suggests the necessity of further investigation of the exact mechanism of the development of diabetes and the cause of abnormalities in the kidney by this certain mutation. Disclosure Y. Fujita: None. T. Hyo: Speaker’s Bureau; Self; ARKRAY, Kissei Pharmaceutical Co., Ltd., LifeScan, Inc., Medtronic, Novo Nordisk Inc. M. Matsubara: None. Y. Hamamoto: Research Support; Self; Sumitomo Dainippon Pharma Co., Ltd. Speaker’s Bureau; Self; Novo Nordisk Inc. D. Tanaka: None. Y. Seino: Research Support; Self; ARKRAY, Bayer Yakuhin, Ltd., Boehringer Ingelheim International GmbH, Eli Lilly Japan K.K., Merck Sharp & Dohme Corp., Nippon Boehringer Ingelheim Co. Ltd., Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Terumo Medical Corporation. Speaker’s Bureau; Self; Becton, Dickinson and Company, Eli Lilly Japan K.K., Kao Corporation, Merck Sharp & Dohme Corp., Nippon Boehringer Ingelheim Co. Ltd., Novo Nordisk Inc., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited.