ISSN : 2146-3123
E-ISSN : 2146-3131

Genetic and Clinical Characterization of Patients with Maturity-Onset of Diabetes of the Young (MODY): Identification of Novel Variations
Esra Arslan Ateş1, Özlem Üstay2, Hamza Polat3, Tuğçe Apaydın2, Onur Elbasan2, Özlem Yıldırım4, Ahmet İlter Güney3
1Genetic Diseases Diagnosis Center, Marmara University Pendik Training and Research Hospital, İstanbul, Turkey
2Department of Endocrinology and Metabolism, Marmara University School of Medicine, İstanbul, Turkey
3Department of Medical Genetics, Marmara University School of Medicine, Istanbul, Turkey
4Department of Molecular Biology and Genetics, İstanbul University, İstanbul, Turkey
DOI : 10.5152/balkanmedj.2021.20155
Pages : 272-277

Background: Maturity-onset diabetes of the young (MODY) is a rare monogenic type of diabetes, and accounts for 2-5% of all diabetes cases. An early age of onset, a family history supporting autosomaldominant inheritance, insulin resistance, and the absence of autoimmunity are the major characteristics of MODY. However, genetic testing is crucial for diagnosis.
Aims: To investigate the 7 MODY-related genes and clinical findings of patients with a preliminary clinical diagnosis of MODY.
Study Design: Retrospective cross-sectional study.
Methods: In this study, 7 genes (KCNJ11, ABCC8, INS, GCK, HNF4A, HNF1A, and HNF1B) related to MODY were screened via targeted sequencing in 182 cases with a confirmed pre-diagnosis of MODY. The clinical characteristics of the patients were evaluated retrospectively.
Results: A total of 182 patients, 48% of whom were women, between the ages of 18-62 were included in the study. In 30 cases (16.4%), 28 different pathogenic variations were found, of which 20 were previously reported and 8 were novel variations segregated by disease within the family. Pathogenic variations were detected in the following genes in order of mutation frequency; GCK, HNF1A, ABCC8, HNF4A, HNF1B and KCNJ11. Interestingly, six of the 30 cases (20%) carried a pathogenic variation in the ABCC8 gene. No mutation was detected in the INS gene. A family history of vertically transmitted diabetes and elevated HbA1C at the time of diagnosis were found in 20 (66%) and 16 (52%) cases, respectively.
Conclusion: In this series, 28 different pathogenic variations are identified, 8 of which are novel. The rate of pathogenic variation in the ABCC8 gene is unexpectedly high. Two-thirds of cases have a family history of vertically transmitted diabetes.

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