We aimed to identify the discriminatory clinical features at diabetes diagnosis of patients with glucokinase (GCK), hepatocyte nuclear factor-1A (HNF1A), and HNF4AMODY in the pediatric population.
In the genetic testing arm, patients with MODY received treatment changes (sulfonylureas for HNF1A- and HNF4A-MODY associated with a 1.0% reduction in HbA<sub>1c</sub>; no treatment for GCK-MODY).
Identification of the HNF4A mutation in the father established a diagnosis of maturity-onset diabetes of the young (MODY), which enabled medication change resulting in improved glycaemic control.
We also interrogated transactivation activities on multiple gene targets by multiple known and novel HNF4α mutants identified in patients with maturity onset diabetes of the young 1 (MODY1) and liver cancer.
Seventeen children had pathogenic/likely pathogenic variants in MODY genes, two diagnosed with type 2 diabetes, four diagnosed with antibody-negative type 1 diabetes (T1DM), three diagnosed with antibody-positive T1DM, and eight previously diagnosed with MODY.
However, positivity for ZnTA can be used as a negative MODY pre-diagnostic criterion even in the region of Central and East Europe, where other islet cell autoantibodies are common in MODY patients.
Dysregulation of HNF4α expression has been associated with many human diseases such as ulcerative colitis, colon cancer, maturity-onset diabetes of the young, liver cirrhosis, and hepatocellular carcinoma.
Among patients with neonatal diabetes (i.e. with onset within first 6 months of life) and patients with Maturity Onset Diabetes of the Young (MODY; an autosomal dominant form of diabetes), those carrying mutations in KCNJ11, ABCC8, HNF1A and HNF4A genes usually respond to oral therapy with sulphonylurea, while those bearing GCK mutations do not necessitate any treatment.
Methods Mutation analysis of MODY genes (GCK, HNF1A, HNF4A, HNF1B, ABCC8, INS and KCNJ11) was performed using targeted NGS in 106 patients with a clinical diagnosis of MODY.
Hepatocyte nuclear factor 4α (HNF4α) has an important role in pancreatic β-cells, and mutations of the human <i>HNF4A</i> gene cause a type of maturity-onset diabetes of the young (MODY1).
We redefine p.R114W as a pathogenic mutation that causes a distinct clinical subtype of HNF4AMODY with reduced penetrance, reduced sensitivity to sulfonylurea treatment, and no effect on birth weight.
Glucokinase monogenic diabetes (GCK-maturity-onset diabetes of the young [MODY]) should be differentiated from gestational diabetes mellitus (GDM) because management differs.
Single doses of 3 mg glipizide and 5 mg glibenclamide/glyburide were administered sequentially to seven HNF1A/HNF4AMODY subjects and six control individuals matched for their age, BMI and CYP2C9 genotype.
We addressed the links between the functional and geographically variable PTPN22 SNPs with MODY manifestation and the expression of islet cell autoantibodies in 276 MODY patients who originated from four regions (the Czech Republic, Israel, Japan and Brazil).
The aim of the present study was to investigate the contribution of maturity-onset diabetes of the young (MODY) genes to the etiology of 14 Chinese MODY families and to assess phenotypic differences between patients with MODY but without a known genetic cause of diabetes (MODYX) and those with early onset type 2 diabetes (T2D).