There are a total of ten cases of both MODY 3 and HCA phenotypes reported in the literature to date; incomplete penetrance for HCA was observed, and all the patients with HCA developed diabetes.
These findings provide a possible explanation for the species difference in disease phenotypes observed with HNF1A mutations and offer mechanistic insights into how the HNF1A gene may also influence type 2 diabetes.
The penetrance of HNF1A variants differs considerably; thus, to assess the genetic risk of diabetes in carrier subjects of a HNF1A mutant allele, a functional characterization of mutant forms is of paramount importance.
Furthermore, studies of N-glycan alterations have successfully been used to identify individuals with rare types of diabetes (such as the HNF1A-MODY), and also to evaluate functional significance of novel diabetes-associated mutations.
In one of the first studies of human pancreatic islets with a disease-causing HNF1A variant associated with the most common form of monogenic diabetes, we found that HNF1A dysfunction leads to insulin-insufficient diabetes reminiscent of T1D by impacting the regulatory processes critical for glucose-stimulated insulin secretion and suggest a rationale for a therapeutic alternative to current treatment.
Hyperinsulinaemic hypoglycaemia in infancy and diabetes in later life have been reported in patients with <i>HNF1A, HNF4A</i> and <i>ABCC8</i> mutations.
This study aimed to investigate differences in serum miR-122 levels in Chinese patients with different forms of diabetes, including T2DM, type 1 diabetes (T1DM), HNF1A variant-induced diabetes (HNF1A-DM), glucokinase variant-induced diabetes (GCK-DM), and mitochondrial A3243G mutation-induced diabetes (MDM).
In a randomised, double-blinded, crossover study, patients with HNF1A-diabetes will randomly be assigned to 16 weeks of treatment with glimepiride+linagliptin, 4 weeks of washout and 16 weeks of treatment with glimepiride+placebo (or vice versa).
Thus, our findings support that the E3 SUMO ligase PIASγ regulates HNF-1A SUMOylation with functional implications, representing new targets for drug development and precision medicine in diabetes.
In this study we aimed to describe the characteristics of young adults diagnosed with diabetes before the age of 45 years, who have rare <i>HNF1A</i> allele variants, and estimate the prevalence of HNF1A-MODY in Croatia.
We hypothesized that common variants at the <i>HNF1A</i> locus (rs1169288 [rs1169288" genes_norm="6927">I27L], rs1800574 [rs1800574" genes_norm="6927">A98V]), which are associated with type 2 diabetes susceptibility, may modify age at diabetes diagnosis in individuals with HNF1A-MODY.
Using traditional criteria (family history of diabetes and onset of diabetes ⩽25 years) and an hs-CRP cut off of ⩽0.5 mg/l, 125 and 37 adults, respectively, were identified for HNF1A gene testing.
Furthermore, T2D genetic risk plays a small role in LADA, with a degree of evidence for the HNF1A locus, highlighting the potential for genetic risk scores to contribute towards defining diabetes subtypes.
Our functional investigations indicate that 0.44% of the population carry HNF1A variants that result in a substantially increased risk for developing diabetes.
We present a family with HNF1A-MODY due to a likely pathogenic mutation in HNF1A (c.59G>A, p.Gly20Glu), diagnosed a long time after the first diagnosis of diabetes.
Mutations in the transcription factors HNF1A and HNF4A and in the β-cell potassium ATP channel components cause diabetes which responds to low dose and high dose sulfonylurea agents, respectively, while glucokinase mutations require no treatment.