PDF(Pubmed)
Abstract：
UNASSIGNED: Monogenic diabetes (MD) is caused by a mutation in a single gene and accounts for approximately 2.5-6% of all diabetes cases. Maturity-onset diabetes of the young (MODY) is the most common form of MD. To date, 14 different genes have been identified and associated with the presence of MODY phenotype. However, the number of potential candidate genes with relevance to beta cell function and glucose metabolism is increasing as more research is published. The aim of the study was to identify potentially causative variants in selected candidate genes in patients with a clinical diagnosis of MD.
UNASSIGNED: Targeted Next-Generation Sequencing (tNGS) on Illumina NextSeq 550 platform involving Agilent SureSelectQXT Target Enrichment protocol for 994 patients with suspected MD was performed. In the next step, the sequencing data of 617 patients with no pathogenic variants in main MD-related genes were reanalysed for the presence of causative variants in six candidate genes (MTOR, TBC1D4, CACNA1E, MNX1, SLC19A2, KCNH6). The presence of the selected variants was confirmed by Sanger sequencing.
UNASSIGNED: Seven heterozygous possibly damaging variants were identified in four candidate genes (MTOR, TBC1D4, CACNA1E, MNX1). Five changes were assessed as novel variants, not previously described in available databases. None of the described variants were present among patients previously diagnosed with MODY diabetes due to causative, pathogenic variants in known MODY-related genes.
UNASSIGNED: The results obtained seem to confirm the effectiveness of the NGS method in identifying potentially causative variants in novel candidate genes associated with MODY diabetes.
UNASSIGNED: Targeted Next-Generation Sequencing (tNGS) on Illumina NextSeq 550 platform involving Agilent SureSelectQXT Target Enrichment protocol for 994 patients with suspected MD was performed. In the next step, the sequencing data of 617 patients with no pathogenic variants in main MD-related genes were reanalysed for the presence of causative variants in six candidate genes (MTOR, TBC1D4, CACNA1E, MNX1, SLC19A2, KCNH6). The presence of the selected variants was confirmed by Sanger sequencing.
UNASSIGNED: Seven heterozygous possibly damaging variants were identified in four candidate genes (MTOR, TBC1D4, CACNA1E, MNX1). Five changes were assessed as novel variants, not previously described in available databases. None of the described variants were present among patients previously diagnosed with MODY diabetes due to causative, pathogenic variants in known MODY-related genes.
UNASSIGNED: The results obtained seem to confirm the effectiveness of the NGS method in identifying potentially causative variants in novel candidate genes associated with MODY diabetes.
摘要：
■单基因糖尿病（MD）是由单个基因的突变引起的，约占所有糖尿病病例的2.5-6％。年轻人的成熟型糖尿病（MODY）是最常见的MD形式。迄今为止,已鉴定了14种不同的基因，并与MODY表型的存在有关。然而,随着越来越多的研究发表，与β细胞功能和葡萄糖代谢相关的潜在候选基因的数量正在增加。该研究的目的是在临床诊断为MD的患者中确定选定的候选基因中的潜在致病变异。
■在IlluminaNextSeq550平台上对994名疑似MD患者进行了涉及AgilentSureSelectQXT目标富集方案的靶向下一代测序(tNGS)。下一步,重新分析了617名在主要MD相关基因中没有致病变异的患者的测序数据，以确定六个候选基因中存在致病变异（MTOR，TBC1D4,CACNA1E,MNX1、SLC19A2、KCNH6)。通过Sanger测序确认所选变体的存在。
■在四个候选基因（MTOR，TBC1D4,CACNA1E,MNX1)。五个变化被评估为新的变体，以前在可用数据库中没有描述。在先前诊断为MODY糖尿病的患者中，由于病因，已知MODY相关基因的致病变异。
■获得的结果似乎证实了NGS方法在鉴定与MODY糖尿病相关的新型候选基因中潜在致病变异中的有效性。
■在IlluminaNextSeq550平台上对994名疑似MD患者进行了涉及AgilentSureSelectQXT目标富集方案的靶向下一代测序(tNGS)。下一步,重新分析了617名在主要MD相关基因中没有致病变异的患者的测序数据，以确定六个候选基因中存在致病变异（MTOR，TBC1D4,CACNA1E,MNX1、SLC19A2、KCNH6)。通过Sanger测序确认所选变体的存在。
■在四个候选基因（MTOR，TBC1D4,CACNA1E,MNX1)。五个变化被评估为新的变体，以前在可用数据库中没有描述。在先前诊断为MODY糖尿病的患者中，由于病因，已知MODY相关基因的致病变异。
■获得的结果似乎证实了NGS方法在鉴定与MODY糖尿病相关的新型候选基因中潜在致病变异中的有效性。
