Hemoglobin A1C can differentiate subjects with GCK mutations among patients suspected to have MODY
Author:
Yılmaz Uzman Ceren1, Erbaş İbrahim Mert2ORCID, Giray Bozkaya Özlem1, Paketçi Ahu2, Çağlayan Ahmet Okay3, Abacı Ayhan3, Kulalı Melike Ataseven1, Böber Ece1, Kekilli Arda3, Çinleti Tayfun1, Erçal Murat Derya13, Demir Korcan2ORCID
Affiliation:
1. Department of Pediatric Genetics , Faculty of Medicine, Dokuz Eylül University , İzmir , Turkey 2. Department of Pediatric Endocrinology , Faculty of Medicine, Dokuz Eylül University , İzmir , Turkey 3. Department of Medical Genetics , Faculty of Medicine, Dokuz Eylül University , İzmir , Turkey
Abstract
Abstract
Objectives
The aim of this study is to determine the clinical and molecular characteristics enabling differential diagnosis in a group of Turkish children clinically diagnosed with MODY and identify the cut-off value of HbA1c, which can distinguish patients with GCK variants from young-onset type 1 and type 2 diabetes.
Methods
The study included 49 patients from 48 unrelated families who were admitted between 2018 and 2020 with a clinical diagnosis of MODY. Clinical and laboratory characteristics of the patients at the time of the diagnosis were obtained from hospital records. Variant analysis of ten MODY genes was performed using targeted next-generation sequencing (NGS) panel and the variants were classified according to American Collage of Medical Genetics and Genomics (ACMG) Standards and Guidelines recommendations.
Results
A total of 14 (28%) pathogenic/likely pathogenic variants were detected among 49 patients. 11 variants in GCK and 3 variants in HNF1A genes were found. We identified four novel variants in GCK gene. Using ROC analysis, we found that best cut-off value of HbA1c at the time of diagnosis for predicting the subjects with a GCK variant among patients suspected to have MODY was 6.95% (sensitivity 90%, specificity 86%, AUC 0.89 [95% CI: 0.783–1]). Most of the cases without GCK variant (33/38 [86%]) had an HbA1c value above this cutoff value. We found that among participants suspected of having MODY, family history, HbA1c at the time of diagnosis, and not using insulin therapy were the most differentiating variables of patients with GCK variants.
Conclusions
Family history, HbA1c at the time of diagnosis, and not receiving insulin therapy were found to be the most distinguishing variables of patients with GCK variants among subjects suspected to have MODY.
Publisher
Walter de Gruyter GmbH
Subject
Endocrinology,Endocrinology, Diabetes and Metabolism,Pediatrics, Perinatology and Child Health
Reference48 articles.
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