Department of Pediatric Endocrinology, Faculty of Medicine, Ege University, Izmir, Turkey.
Department of Pediatric Genetics, Faculty of Medicine, Ege University, Izmir, Turkey.
Diabetes Res Clin Pract. 2023 Nov;205:110953. doi: 10.1016/j.diabres.2023.110953. Epub 2023 Oct 13.
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).
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.
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.
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.
我们旨在通过靶向下一代测序（NGS）和全外显子组测序（WES），研究单基因糖尿病（DM）的分子遗传基础和新的候选致病基因。
本研究纳入了 100 例具有单基因 DM 的临床特征和家族史的患者。使用包括 14 个基因的 NGS 面板进行分子分析。在未检测到变异的情况下，计划进行 WES。
在 35 例（35%）采用靶向 NGS 方法的患者中检测到 30 个不同基因中的 30 个致病变异。最常见的致病性变异是在 GCK 基因中，在 25 例（25%）患者中发现。在 4 例（4%）ABCC8 基因患者中检测到 4 个不同的变异。在 65 例中的 45 例中进行了 WES 分析。在一名偶发高血糖患者的 IFIH1 基因中检测到杂合 c.2635C>T(p.Gln879Ter)变异。在分离分析中，受影响的母亲表现为该变异的杂合子。
通过 NGS 靶向面板确定了 35%的病例的分子病因。在单基因 DM 基因中发现了 17 个新的变异。在本研究中，通过 WES 分析确定了一个无法通过 NGS 面板诊断的病例的候选基因。
