Molecular diagnosis in patients with monogenic diabetes mellitus, and detection of a novel candidate gene.

Autor: Goksen D; Department of Pediatric Endocrinology, Faculty of Medicine, Ege University, Izmir, Turkey., Evin F; Department of Pediatric Endocrinology, Faculty of Medicine, Ege University, Izmir, Turkey., Isik E; Department of Pediatric Genetics, Faculty of Medicine, Ege University, Izmir, Turkey. Electronic address: esrabadak36@gmail.com., Ozen S; Department of Pediatric Endocrinology, Faculty of Medicine, Ege University, Izmir, Turkey., Atik T; Department of Pediatric Genetics, Faculty of Medicine, Ege University, Izmir, Turkey., Ozkinay F; Department of Pediatric Endocrinology, Faculty of Medicine, Ege University, Izmir, Turkey., Akcan N; Department of Pediatric Endocrinology, Faculty of Medicine, Near East University, Nicosia, Cyprus., Ozkan B; Department of Pediatric Endocrinology, Dr Behçet Uz Çocuk Training and Research Hospital, Izmir, Turkey., Buyukinan M; Department of Pediatric Endocrinology, Konya Training and Research Hospital, Konya, Turkey., Nuri Ozbek M; Department of Pediatric Endocrinology, Mardin Artuklu University, Mardin, Turkey., Darcan S; Department of Pediatric Endocrinology, Faculty of Medicine, Ege University, Izmir, Turkey., Onay H; Multigen Genetic Diseases Diagnosis Center, Izmir, Turkey.
Jazyk: angličtina
Zdroj: Diabetes research and clinical practice [Diabetes Res Clin Pract] 2023 Nov; Vol. 205, pp. 110953. Date of Electronic Publication: 2023 Oct 13.
DOI: 10.1016/j.diabres.2023.110953
Abstrakt: Aim: We aimed to investigate molecular genetic basis of monogenic diabetes (DM) and novel responsible candidate genes with targeted Next Generation Sequencing (NGS) and Whole Exome Sequencing (WES).
Methods: A hundred cases presenting with clinical findings and a family history of monogenic DM were included in the study. Molecular analysis was performed using an NGS panel including 14 genes. Following targeted NGS, WES was planned in cases in whom no variant was detected.
Results: Thirty different disease-causing variants in seven different genes were detected in thirty-five (35 %) cases with targeted NGS approach. Most common pathogenic variant was found in GCK gene in 25 (25 %) cases. Four different variants were detected in 4 (4 %) patients in ABCC8 gene. In 45 of 65 cases; WES analyses were done. A heterozygous c.2635C > T(p.Gln879Ter) variant was detected in IFIH1 gene in a patient with incidental hyperglycemia. In the segregation analysis affected mother was shown to be heterozygous for the same variant.
Conclusion: Molecular etiology was determined in 35 % cases with the NGS targeted panel. Seventeen novel variants in monogenic DM genes have been identified. A candidate gene determined by WES analysis in a case that could not be diagnosed with NGS panel in this study.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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