The HNF1B mutations and deletion associated with diabetes and their resulting diabetic phenotypes: a systematic review

Mutations or deletion in HNF1B gene has been found to be related to a special type of monogenetic diabetes (HNF1B-DM). However, the phenotypic features of HNF1B-DM and the related gene abnormalities remain unclear.

We systemically reviewed the literature associated with HNF1B-DM in PubMed, China National Knowledge Infrastructure (CNKI), and Wanfang databases. The mutations and clinical data of HNF1B-DM were recorded. The phenotypes between mutations and deletion in HNF1B were analyzed.

In total, 261 eligible individuals were included. 64 mutations were reported in 134 patients, and another 127 patients carried a large deletion in HNF1B gene. The mutations were distributed throughout from exons 1 to 7, including missense, nonsense, frameshift, and splice site mutation. Body weight index (BMI) was available for 69 patients; 55 patients (79.7%) were normal or underweight. Of the 131 patients with available family history, 105 (80.2%) reported a family history of diabetes. Data on age at diagnosis of diabetes was recorded in 210 patients with a mean of 23.7 years. Estimated glomerular filtration rate was recorded in 52 patients with a median of 47.00 ml/min per 1.73 m². Renal cysts were in 78.9%, pancreatic dysplasia in 78.6%, and hypomagnesemia in 64.3% of the patients. The patients with HNF1B deletion had different diabetic phenotypes from the patients with HNF1B point mutation.

HNF1B-DM patients were with younger onset age, normal or low BMI, renal cyst, pancreatic dysplasia, and hypomagnesemia. The patients should be recommended for genetic testing to differentiate HNF1BDM from other young-onset diabetes earlier.