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Mutations in the Hepatocyte Nuclear Factor 1 Alpha (HNF1A), 4 Alpha (HNF4A) and 1 Beta (HNF1B) in Maturity-Onset Diabetes of the Young in Croatia

Authors: Caban, Domagoj; Merkler Šorgić, Ana; Ljubić, Hana; Špehar Uroić, Anita; Krnić, Nevena; Smirčić-Duvnjak, Lea; Kaštelan, Darko; +1 Authors

Mutations in the Hepatocyte Nuclear Factor 1 Alpha (HNF1A), 4 Alpha (HNF4A) and 1 Beta (HNF1B) in Maturity-Onset Diabetes of the Young in Croatia

Abstract

Introduction: Maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes that is characterized by an early onset (usually before 25 years), autosomal dominant mode of inheritance and a primary defect in pancreatic β-cell function. MODY is a common form of monogenic diabetes and it may account for 1% to 2% of all diabetes cases in Europe. Many people with MODY are misdiagnosed with type 1 or type 2 diabetes. Materials and Methods: All adult subjects with diabetes onset under age of 45 years and currently older than 18 years. Other inclusion criteria are: evidence of endogenous insulin secretion (fasting or random C-peptide ≥ 0.2 nmol/L) and negative glutamic acid decarboxylase antibodies (GADA), islet cell autoantibodies (ICA) and islet tyrosine phosphatase 2 (IA2). We analysed 44 patients for HNF1A-MODY, 14 patients for HNF4A-MODY and 8 patients for HNF1B-MODY. For identification of mutations in the coding and promoter region of analyzed genes, we used the Sanger sequencing method. Results: We identified six different mutations in nine patients for subtype HNF1A-MODY. These mutations are located in exons 2, 3, 4 and 6, but the greatest number are found in exon 4, p.Gly292Argfs*25. For subtype HNF1B-MODY we identified one mutation, p.Val458Gly in exon 7. No HNF4A-MODY gene mutations were identified in any of patients analyzed. Conclusions: Correctly identifying MODY has important implications for treatment, surveillance of complications and associated extra-pancreatic disorders, and identification of affected and at- risk family members.

Keywords

Sanger sequencing, diabetes, MODY

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
0
Average
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