Introduction Monogenic diabetes is attributed to genetic variations in a single gene. Maturity-onset diabetes of the young (MODY) is the most common phenotype associated with monogenic diabetes, but is frequently misdiagnosed as either type 1 or type 2 diabetes. Increasing our basic understanding of genetic variations in MODY may help to improve the accuracy of providing the correct diagnosis and personalize subsequent treatment regimens in different racial populations. For this reason, this study was designed to identify nucleotide variants in early onset diabetes patients with clinically suspected MODY in a Korean population. Research design and methods Among 2908 Korean patients diagnosed with diabetes, we selected 40 patients who were diagnosed before 30 years old and were clinically suspected of MODY. Genetic testing was performed using a targeted gene sequencing panel that included 30 known monogenic diabetes genes. The pathogenicity of the identified variants was assessed according to the American College of Medical Genetics and Genomics and Association for Molecular Pathology (ACMG-AMP) guidelines. Results A total of six rare missense variants (p.Ala544Thr in HNF1A, p.Val601Ile and p.His103Tyr in ABCC8, p.Pro33Ala in PDX1, p.Gly18Glu in INS, and p.Arg164Gln in PAX4) in five distinct MODY genes were identified in five patients. In addition, a variant was identified in mitochondrial DNA at 3243A>G in one patient. The identified variants were either absent or detected at a rare frequency in the 1000 Genomes Project. These variants were classified as uncertain significance using the ACMG-AMP guidelines. Conclusion Using a targeted gene sequencing panel, we identified seven variants in either MODY genes or mitochondrial DNA using a Korean patient population with early onset diabetes who were clinically suspected of MODY. This genetic approach provides the ability to compare distinct populations of racial and ethnic groups to determine whether specific gene is involved in their diagnosis of MODY. Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as supplemental information. If there are requests for data sharing, contact to corresponding author by email (tgohkjs@chungbuk.ac.kr).

中文翻译：

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使用靶向面板测序在早发性糖尿病患者中鉴定单基因糖尿病的候选基因变异

简介 单基因糖尿病归因于单个基因的遗传变异。年轻成人发病型糖尿病 (MODY) 是与单基因糖尿病相关的最常见表型，但经常被误诊为 1 型或 2 型糖尿病。增加我们对 MODY 遗传变异的基本了解可能有助于提高在不同种族人群中提供正确诊断和个性化后续治疗方案的准确性。因此，本研究旨在鉴定韩国人群中临床疑似 MODY 的早发糖尿病患者的核苷酸变异。研究设计与方法 在2908名韩国确诊糖尿病患者中，我们选取​​40名30岁前确诊且临床疑似MODY的患者。使用包含 30 个已知单基因糖尿病基因的靶向基因测序面板进行基因检测。根据美国医学遗传学和基因组学学院和分子病理学协会 (ACMG-AMP) 指南评估了已鉴定变异的致病性。结果 共有 6 个罕见的错义变异（HNF1A 中的 p.Ala544Thr、ABCC8 中的 p.Val601Ile 和 p.His103Tyr、PDX1 中的 p.Pro33Ala、INS 中的 p.Gly18Glu 和 PAX4 中的 p.Arg164Gln）在五个不同的 MODY 基因中被发现在五名患者中发现。此外，在一名患者的线粒体 DNA 中发现了 3243A>G 的变异。在 1000 基因组计划中，已识别的变异要么不存在，要么以罕见的频率检测到。使用 ACMG-AMP 指南将这些变体归类为不确定的显着性。结论 使用靶向基因测序面板，我们使用韩国临床怀疑患有 MODY 的早发糖尿病患者人群鉴定了 MODY 基因或线粒体 DNA 中的 7 个变异。这种遗传方法提供了比较不同种族和族裔群体的能力，以确定特定基因是否参与了他们的 MODY 诊断。可应合理要求提供数据。与研究相关的所有数据都包含在文章中或作为补充信息上传。如果有数据共享请求，请通过电子邮件联系通讯作者（tgohkjs@chungbuk.ac.kr）。这种遗传方法提供了比较不同种族和族裔群体的能力，以确定特定基因是否参与了他们的 MODY 诊断。可应合理要求提供数据。与研究相关的所有数据都包含在文章中或作为补充信息上传。如果有数据共享请求，请通过电子邮件联系通讯作者（tgohkjs@chungbuk.ac.kr）。这种遗传方法提供了比较不同种族和族裔群体的能力，以确定特定基因是否参与了他们的 MODY 诊断。可应合理要求提供数据。与研究相关的所有数据都包含在文章中或作为补充信息上传。如果有数据共享请求，请通过电子邮件联系通讯作者（tgohkjs@chungbuk.ac.kr）。