A Comprehensive Analysis of Hungarian MODY Patients-Part II: Glucokinase MODY Is the Most Prevalent Subtype Responsible for about 70% of Confirmed Cases.

Zsolt Gaál,Enikő Felszeghy,László Madar,Irén Kántor,Péter Tóth-Heyn,Zsuzsanna Karádi,Zsuzsanna Szűcs,Andrea Luczay,Orsolya Benn,István Balogh

doi:10.3390/life11080771

Abstract

MODY2 is caused by heterozygous inactivating mutations in the glucokinase (GCK) gene that result in persistent, stable and mild fasting hyperglycaemia (5.6–8.0 mmol/L, glycosylated haemoglobin range of 5.6–7.3%). Patients with GCK mutations usually do not require any drug treatment, except during pregnancy. The GCK gene is considered to be responsible for about 20% of all MODY cases, transcription factors for 67% and other genes for 13% of the cases. Based on our findings, GCK and HNF1A mutations together are responsible for about 90% of the cases in Hungary, this ratio being higher than the 70% reported in the literature. More than 70% of these patients have a mutation in the GCK gene, this means that GCK-MODY is the most prevalent form of MODY in Hungary. In the 91 index patients and their 72 family members examined, we have identified a total of 65 different pathogenic (18) and likely pathogenic (47) GCK mutations of which 28 were novel. In two families, de novo GCK mutations were detected. About 30% of the GCK-MODY patients examined were receiving unnecessary OAD or insulin therapy at the time of requesting their genetic testing, therefore the importance of having a molecular genetic diagnosis can lead to a major improvement in their quality of life.

Highlights

IntroductionGene encoding a key regulator glycolytic enzyme of the hexokinase family [1]
GCK and HNF1A mutations together were responsible for about 90% of the cases, this ratio being higher in Hungary than the 70% reported in the literature [15]
More than 70% of these patients have a mutation in the GCK gene, which means that GCK-MODY

Summary

Introduction

Gene encoding a key regulator glycolytic enzyme of the hexokinase family [1]. It has two tissue-specific promoters and a different exon 1, the upstream promoter being functional in the pancreas (exon 1a) and brain, while the downstream one only in the liver (exons 1b and 1c), resulting in different isoforms of the GCK gene [2,3]. GCK has an important role in carbohydrate metabolism. It is responsible for the catalysis of the first reaction of the glycolytic pathway, the glucose phosphorylation [1]. GCK acts as a glucose sensor of the pancreatic beta-cells [1], it is critical in the process of the regulation of insulin secretion and release

Methods

Results

Conclusion