Identification of causative gene variants for patients with known monogenic diabetes using a targeted next-generation sequencing panel in a single-center study.

Autor: Takase K; Department of Neurology, Hematology, Metabolism, Endocrinology and Diabetology, Faculty of Medicine, Yamagata University, 2-2-2 Iida-nishi, Yamagata, 990-9585 Japan., Susa S; Department of Neurology, Hematology, Metabolism, Endocrinology and Diabetology, Faculty of Medicine, Yamagata University, 2-2-2 Iida-nishi, Yamagata, 990-9585 Japan., Sato H; Genomic Information Analysis Unit, Department of Genomic Cohort Research, Faculty of Medicine, Yamagata University, 2-2-2 Iida-nishi, Yamagata, 990-9585 Japan., Hada Y; Department of Neurology, Hematology, Metabolism, Endocrinology and Diabetology, Faculty of Medicine, Yamagata University, 2-2-2 Iida-nishi, Yamagata, 990-9585 Japan., Nagaoka K; Department of Neurology, Hematology, Metabolism, Endocrinology and Diabetology, Faculty of Medicine, Yamagata University, 2-2-2 Iida-nishi, Yamagata, 990-9585 Japan., Takakubo N; Department of Neurology, Hematology, Metabolism, Endocrinology and Diabetology, Faculty of Medicine, Yamagata University, 2-2-2 Iida-nishi, Yamagata, 990-9585 Japan.; Takakubo Clinic, 2-9-7 Kitamachi, Warabi, Saitama 335-0001 Japan., Karasawa S; Department of Neurology, Hematology, Metabolism, Endocrinology and Diabetology, Faculty of Medicine, Yamagata University, 2-2-2 Iida-nishi, Yamagata, 990-9585 Japan., Kameda W; Department of Neurology, Hematology, Metabolism, Endocrinology and Diabetology, Faculty of Medicine, Yamagata University, 2-2-2 Iida-nishi, Yamagata, 990-9585 Japan., Numakura C; Department of Pediatrics and Clinical Genomics, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama, Saitama 350-0495 Japan., Ishizawa K; Department of Neurology, Hematology, Metabolism, Endocrinology and Diabetology, Faculty of Medicine, Yamagata University, 2-2-2 Iida-nishi, Yamagata, 990-9585 Japan.
Jazyk: angličtina
Zdroj: Diabetology international [Diabetol Int] 2023 Nov 15; Vol. 15 (2), pp. 203-211. Date of Electronic Publication: 2023 Nov 15 (Print Publication: 2024).
DOI: 10.1007/s13340-023-00669-3
Abstrakt: Aims: We aimed to verify the usefulness of targeted next-generation sequencing (NGS) technology for diagnosing monogenic diabetes in a single center.
Methods: We designed an amplicon-based NGS panel targeting 34 genes associated with known monogenic diabetes and performed resequencing in 56 patients with autoantibody-negative diabetes mellitus diagnosed at < 50 years who had not been highly obese. By bioinformatic analysis, we filtered significant variants based on allele frequency (< 0.005 in East Asians) and functional prediction. We estimated the pathogenicity of each variant upon considering the family history.
Results: Overall, 16 candidate causative variants were identified in 16 patients. Among them, two previously known heterozygous nonsynonymous single-nucleotide variants associated with monogenic diabetes were confirmed as causative variants: one each in the GCK and WFS1 genes. The former was found in two independent diabetes-affected families. Two novel putatively deleterious heterozygous variants were also assumed to be causative from the family history: one frameshift and one nonsynonymous single-nucleotide variant in the HNF4A gene. Twelve variants remained as candidates associated with the development of diabetes.
Conclusion: Targeted NGS panel testing was useful to diagnose various forms of monogenic diabetes in combination with familial analysis, but additional ingenuity would be needed for practice.
Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-023-00669-3.
Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest.
(© The Japan Diabetes Society 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)
Databáze: MEDLINE
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