Abstract：
OBJECTIVE: 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.
CONCLUSIONS: 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.
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.
CONCLUSIONS: 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.
摘要：
目的：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）的分子遗传学基础和新的负责任的候选基因。
方法：本研究纳入了100例有单基因DM临床表现和家族史的病例。使用包括14个基因的NGS组进行分子分析。在目标NGS之后，计划在未检测到变异的情况下进行WES。
结果：用靶向NGS方法在35例病例中检测到了7种不同基因中的30种不同的致病变异。在25例（25％）的GCK基因中发现了最常见的致病变异。在4例(4%)患者中检测到ABCC8基因的四种分歧变异。在65例中的45例中，进行了WES分析。杂合c.2635C>T（p。在偶然高血糖患者的IFIH1基因中检测到Gln879Ter）变异。在分离分析中，受影响的母亲对于相同的变体显示为杂合的。
结论：在35％的NGS靶向组病例中确定了分子病因。已经鉴定了单基因DM基因中的17种新变体。在本研究中不能用NGS组诊断的病例中通过WES分析确定的候选基因。
方法：本研究纳入了100例有单基因DM临床表现和家族史的病例。使用包括14个基因的NGS组进行分子分析。在目标NGS之后，计划在未检测到变异的情况下进行WES。
结果：用靶向NGS方法在35例病例中检测到了7种不同基因中的30种不同的致病变异。在25例（25％）的GCK基因中发现了最常见的致病变异。在4例(4%)患者中检测到ABCC8基因的四种分歧变异。在65例中的45例中，进行了WES分析。杂合c.2635C>T（p。在偶然高血糖患者的IFIH1基因中检测到Gln879Ter）变异。在分离分析中，受影响的母亲对于相同的变体显示为杂合的。
结论：在35％的NGS靶向组病例中确定了分子病因。已经鉴定了单基因DM基因中的17种新变体。在本研究中不能用NGS组诊断的病例中通过WES分析确定的候选基因。
