Zhou Qiaoli, Samadli Sama, Zhang Haoyu, Zheng Xueqin, Zheng Bixia, Zhang Aihua, Gu Wei
Department of Endocrinology, Children's Hospital of Nanjing Medical University, Nanjing, China.
Nanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing, China.
J Clin Endocrinol Metab. 2024 Nov 6. doi: 10.1210/clinem/dgae779.
Single gene variants that give rise to neonatal diabetes mellitus (NDM), maturity onset diabetes of the young (MODY) and syndromic forms of diabetes mellitus (SDM) are responsible for 3.1-4.2% of all diabetes cases. This single-center study with a relatively larger sample size aimed to evaluate the clinical and genetic characteristics of Chinese children with suspected monogenic diabetes (MD) using next generation sequencing (NGS) methods.
Data were collected from 1550 consecutive children diagnosed with diabetes/hyperglycemia at the Endocrinology Department of Children's Hospital of Nanjing Medical University from 2012 to 2023. The genotype and phenotype of 138 children with suspected MD were retrospectively analyzed.
Among 138 children, 16, 97, and 25 patients with NDM, suspected MODY and SDM were assessed by NGS, with a pick-up rate of 87.5%, 57.8%, and 56%, respectively. In total, there was a high pick-up rate of MD, with 58% (80 of 138) among antibody-negative pediatric patients. Pathogenic variants were found in GCK, HNF1A, INS, KCNJ11, INSR, HNF4A, ABCC8, WFS1, ALMS1, HNF1B, BLK and ZFP57 genes with 13 novel variants in addition to 4 patients with CNVs. In this cohort, GCK-MODY was the leading cause and the mildest type of MODY. GCK-MODY displayed favorable lipid profile when compared to non-GCK-MODY and MODYX, which might be cardioprotective. Following an accurate genetic diagnosis of diabetes, 19 patients switched from insulin therapy to oral agents or lifestyle interventions.
NGS tests helped to identify the precise etiology of monogenic diabetic patients which has implications for better individualized management.
导致新生儿糖尿病（NDM）、青年发病的成年型糖尿病（MODY）和综合征型糖尿病（SDM）的单基因变异占所有糖尿病病例的3.1%-4.2%。这项样本量相对较大的单中心研究旨在使用下一代测序（NGS）方法评估疑似单基因糖尿病（MD）的中国儿童的临床和遗传特征。
收集了2012年至2023年在南京医科大学附属儿童医院内分泌科连续诊断为糖尿病/高血糖的1550名儿童的数据。对138名疑似MD儿童的基因型和表型进行回顾性分析。
在138名儿童中，分别对16例NDM、97例疑似MODY和25例SDM患者进行了NGS评估，检出率分别为87.5%、57.8%和56%。总体而言，MD的检出率较高，在抗体阴性的儿科患者中占58%（138例中的80例）。在GCK、HNF1A、INS、KCNJ11、INSR、HNF4A、ABCC8、WFS1、ALMS1、HNF1B、BLK和ZFP57基因中发现了致病变异，除4例拷贝数变异（CNV）患者外，还有13个新变异。在该队列中，GCK-MODY是MODY的主要病因且是最轻型的类型。与非GCK-MODY和MODYX相比，GCK-MODY的血脂谱较好，可能具有心脏保护作用。在对糖尿病进行准确的基因诊断后，19名患者从胰岛素治疗改为口服药物或生活方式干预。
NGS检测有助于确定单基因糖尿病患者的确切病因，这对更好的个体化管理具有重要意义。
