Özdemir Taha R, Kırbıyık Özgür, Dündar Bumin N, Abacı Ayhan, Kaya Özge Ö, Çatlı Gönül, Özyılmaz Berk, Acar Sezer, Koç Altuğ, Güvenç Merve S, Kutbay Yaşar B, Erdoğan Kadri M
Health Sciences University Izmir Tepecik Training and Research Hospital, Genetic Diagnostic Center, Izmir, Turkey.
Department of Pediatric Endocrinology, Faculty of Medicine, Izmir Katip Celebi University, Izmir, Turkey.
J Pediatr Endocrinol Metab. 2018 Dec 19;31(12):1295-1304. doi: 10.1515/jpem-2018-0184.
Background Maturity-onset diabetes of the young (MODY) is a common form of monogenic diabetes. Fourteen genes have been identified, each leading to cause a different type of MODY. The aims of this study were to reveal both known and novel variants in MODY genes in patients with MODY using targeted next generation sequencing (NGS) and to present the genotype-phenotype correlations. Methods Mutation analysis of MODY genes (GCK, HNF1A, HNF4A, HNF1B, ABCC8, INS and KCNJ11) was performed using targeted NGS in 106 patients with a clinical diagnosis of MODY. The variants were evaluated according to American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines recommendations. Results A total of 18 (17%) variants were revealed among all patients. Seven variants in GCK, six in HNF4A, four in HNF1A and one in ABCC8 genes were found. Eight of them were previously published and 10 of them were assessed as novel pathogenic or likely pathogenic variants. Conclusions While the most frequent mutations are found in the HNF1A gene in the literature, most of the variants were found in the GCK gene in our patient group using the NGS method, which allows simultaneous analysis of multiple genes in a single panel.
背景 青年发病的成年型糖尿病（MODY）是单基因糖尿病的一种常见形式。已鉴定出14个基因，每个基因都会导致不同类型的MODY。本研究的目的是使用靶向新一代测序（NGS）揭示MODY患者MODY基因中的已知和新变异，并呈现基因型与表型的相关性。方法 对106例临床诊断为MODY的患者使用靶向NGS对MODY基因（GCK、HNF1A、HNF4A、HNF1B、ABCC8、INS和KCNJ11）进行突变分析。根据美国医学遗传学与基因组学学会（ACMG）标准和指南建议对变异进行评估。结果 在所有患者中共发现18个（17%）变异。在GCK基因中发现7个变异，在HNF4A基因中发现6个，在HNF1A基因中发现4个，在ABCC8基因中发现1个。其中8个先前已发表，10个被评估为新的致病或可能致病变异。结论 虽然文献中最常见的突变发现于HNF1A基因，但在我们的患者组中，使用可在单个检测板中同时分析多个基因的NGS方法，大多数变异发现于GCK基因。
