Department of Clinical Genetics, Medical University of Lodz, Lodz, Poland.
Department of Clinical Genetics, Medical University of Lodz, Lodz, Poland.
Diabetes Res Clin Pract. 2022 Jan;183:109154. doi: 10.1016/j.diabres.2021.109154. Epub 2021 Nov 24.
Monogenic diabetes (MD) represents 5-7% of antibody-negative diabetes cases and is a heterogeneous group of disorders.
We used targeted next-generation sequencing (NGS) on Illumina NextSeq 550 platform involving the SureSelect assay to perform genetic and clinical characteristics of a study group of 684 individuals, including 542 patients referred from 12 Polish Diabetes Centers with suspected MD diagnosed between December 2016 and December 2019 and their 142 family members (FM).
In 198 probands (36.5%) and 66 FM (46.5%) heterozygous causative variants were confirmed in 11 different MD-related genes, including 31 novel mutations, with the highest number in the GCK gene (206/264), 22/264 in the HNF1A gene and 8/264 in the KCNJ11 gene. Of the 183 probands with MODY1-5 diabetes, 48.6% of them were diagnosed at the pre-diabetes stage and most of them (68.7%) were on diet only at the time of genetic diagnosis, while 31.3% were additionally treated with oral hypoglycaemic drugs and/or insulin.
In summary, the results obtained confirm the efficacy of targeted NGS method in the molecular diagnosis of patients with suspected MD and broaden the spectrum of new causal variants, while updating our knowledge of the clinical features of patients defined as having MD.
单基因糖尿病（MD）占抗体阴性糖尿病病例的 5-7%，是一组异质性疾病。
我们使用靶向下一代测序（NGS）在 Illumina NextSeq 550 平台上进行，涉及 SureSelect 检测，对包括 542 名来自 12 个波兰糖尿病中心的疑似 MD 患者和 142 名其亲属（FM）在内的 684 名个体进行了遗传和临床特征研究。这些患者于 2016 年 12 月至 2019 年 12 月间确诊。
在 198 名先证者（36.5%）和 66 名 FM（46.5%）中，在 11 个不同的 MD 相关基因中确认了杂合致病变异，包括 31 个新突变，其中 GCK 基因（206/264）、HNF1A 基因（22/264）和 KCNJ11 基因（8/264）的突变数量最多。在 183 名 MODY1-5 糖尿病先证者中，48.6%的患者在糖尿病前期被诊断出来，其中大多数（68.7%）在进行基因诊断时仅接受饮食治疗，而 31.3%的患者还接受了口服降糖药和/或胰岛素治疗。
总之，研究结果证实了靶向 NGS 方法在疑似 MD 患者分子诊断中的有效性，并扩大了新的致病变异谱，同时更新了我们对被定义为 MD 患者的临床特征的认识。
