Maturity onset diabetes of the young due to HNF1A variants in Croatia

Abstract

IntroductionMaturity onset diabetes of the young due to HNF1A mutations (HNF1A-MODY) is the most frequent form of monogenic diabetes in adults. It is often misdiagnosed as type 1 or type 2 diabetes, but establishing genetic diagnosis is important, as treatment differs from the common types of diabetes. HNF1A-MODY has not been investigated in Croatia before due to limited access to genetic testing. In this study we aimed to describe the characteristics of young adults diagnosed with diabetes before the age of 45 years, who have rare HNF1A allele variants, and estimate the prevalence of HNF1A-MODY in Croatia.Materials and methodsWe recruited 477 C-peptide positive and beta cell antibody negative subjects through the Croatian Diabetes Registry. HNF1A was sequenced for all participants and systematic assessment of the variants found was performed. The prevalence of HNF1A-MODY was calculated in the study group and results extrapolated to estimate the proportion of diabetic individuals with HNF1A-MODY in Croatia and the population prevalence.ResultsOur study identified 13 individuals harbouring rare HNF1A allelic variants. After systematic assessment, 8 were assigned a diagnosis of HNF1A-MODY. Two individuals were able to discontinue insulin treatment following the diagnosis. We estimated that HNF1A-MODY in Croatia has a prevalence of 66 (95% CI 61 - 72) cases per million.ConclusionsThe estimated prevalence of HNF1A-MODY in Croatia is similar to that reported in other European countries. Finding cases lead to important treatment changes for patients. This strongly supports the introduction of diagnostic genetic testing for monogenic diabetes in Croatia.

Plasma Fucosylated Glycans and C-Reactive Protein as Biomarkers of HNF1A-MODY in Young Adult–Onset Nonautoimmune Diabetes

“…A GP30 cutoff of 0.70% missed only 2 of 16 probands with likely damaging HNF1A alleles. If GP30 was used as a selective tool for (41). †Allele present in two unrelated probands from U.K. and Croatian cohort.…”

Association of Common Variants in HNF1A Gene with Serum AFP Level in Healthy Chinese Individuals and HCC Patients

“…Previous studies showed that AFP promoter mutations in the distal HNF1-binding region and the proximal HNF1-binding region play important roles in regulating AFP expression [12,13]. Currently, HNF1A gene variants are associated with maturity onset diabetes of the young (MODY) [14,15], Creactive protein (CRP) levels [16][17][18], gamma-glutamyl transferase (GGT) levels [19,20], total cholesterol (TC) levels [21], pancreatic cancer [22], coronary artery disease [21,23], and metabolic syndrome (MS) [24]. The most common variants in HNF1A are rs1169288 (A/C, Ile27Leu), rs2464196 (G/A, Ser487Asn), and rs1169310 (C/T), which have been reported to be associated with the CRP level, coronary artery disease, and diabetic retinopathy [17,18,25,26].…”

Homozygous Hypomorphic HNF1A Alleles Are a Novel Cause of Young-Onset Diabetes and Result in Sulfonylurea-Sensitive Diabetes

“…A heterozygous relative of the proband developed diabetes later in life, at age 80 years. Although hs-CRP levels were low in the three carriers studied, the level of fucosylated glycan GP30 (low levels of which are predictive of HNF1A mutations) was above the cutoff in two of the three (18). In another study, a heterozygous proband received a diagnosis at age 39 years and had a BMI of 27 kg/m 2 .…”

“…The p.A251T HNF1A variant has been reported in two studies describing heterozygous carriers (17,18), bringing the total number of reported heterozygous carriers to eight. In the study by Thanabalasingham et al (17), the proband, who presented with diabetes at the age of 43 years, was managed with metformin and sulfonylurea therapy for 25 years.…”