Screening of diabetes of youth for hepatocyte nuclear factor 1 mutations: clinical phenotype of HNF1β-related maturity-onset diabetes of the young and HNF1α-related maturity-onset diabetes of the young in Japanese.

Aim: To compare the prevalence and clinical features of HNF1β-related MODY and HNF1α-related MODY in Japanese.

Methods: We enrolled 230 Japanese patients with suspected MODY and examined them for HNF1α and HNF1β mutations. We characterized the clinical features of HNF1β-related MODY (HNF1β-MODY) and HNF1α-related MODY (HNF1α-MODY).

Results: Six patients had HNF1β mutations, four of which were large gene deletions and 24 patients had HNF1α mutations, which included one gene deletion. The mean fasting plasma glucose level at onset of HNF1β-MODY was considerably higher and the age of onset of HNF1β-MODY was considerably older than they were for HNF1α-MODY, while the mean BMI and C-peptide index at onset were similar. Three patients with HNF1β-MODY were found to have dorsal pancreatic agenesis and four of them had whole-gene deletion. Five of the patients with HNF1β-MODY had insulin secretion defects and were treated with insulin, and four of these did not have a parent with overt diabetes.

Conclusion: HNF1β-MODY may present as β-cell dysfunction in Japanese rather than as hyperinsulinaemia, which it does among European/American. This dysfunction might result from an intrinsically lower capacity for insulin secretion in Japanese. HNF1β-MODY has an older age of onset than HNF1α-MODY, which may suggest lower penetrance of the disease. In addition, HNF1β-MODY has a broad spectrum of clinical manifestations, some of which are detectable by imaging. This may be helpful in some cases for selecting HNF1β-MODY candidates for genetic testing.