Institute of Molecular Genetics and Genetic Engineering, Belgrade, Serbia and Montenegro.
Division of endocrinology, University Children's Hospital, Belgrade, Serbia and Montenegro.
Endokrynol Pol. 2019;70(1):28-36. doi: 10.5603/EP.a2018.0064. Epub 2018 Sep 27.
Maturity onset diabetes of the young (MODY) is a rare form of monogenic diabetes. Being clinically and genetically heterogeneous, it is often misdiagnosed as type 1 or type 2 diabetes, leading to inappropriate therapy. MODY is caused by a single gene mutation. Thirteen genes, defining 13 subtypes, have been identified to cause MODY. A correct diagnosis is important for the right therapy, prognosis, and genetic counselling.
Twenty-nine unrelated paediatric patients clinically suspected of having MODY diabetes were analysed using TruSight One panel for next-generation sequencing (NGS) and multiplex ligation-dependent probe amplification (MLPA) assay.
In this study we identified variants in MODY genes in 22 out of 29 patients (75.9%). Using two genetic tests, NGS and MLPA, we detected both single nucleotide variants and large deletions in patients. Most of the patients harboured a variant in the GCK gene (11/22), followed by HNF1B (5/22). The rest of the variants were found in the NEUROD1 and HNF1A genes. We identified one novel variant in the GCK gene: c.596T>C, p.Val199Ala. The applied genetic tests excluded the suspected diagnosis of MODY in two patients and revealed variants in other genes possibly associated with the patient's clinical phenotype.
In our group of MODY patients most variants were found in the GCK gene, followed by variants in HNF1B, NEUROD1, and HNF1A genes. The combined NGS and MLPA-based genetic tests presented a comprehensive approach for analysing patients with suspected MODY diabetes and provided a successful differential diagnosis of MODY subtypes.
青少年起病的成年型糖尿病（MODY）是一种罕见的单基因糖尿病。由于临床表现和遗传学上的异质性，它常被误诊为 1 型或 2 型糖尿病，导致治疗不当。MODY 是由单个基因突变引起的。已经确定了 13 个基因，定义了 13 个亚型，这些基因导致 MODY。正确的诊断对于正确的治疗、预后和遗传咨询都很重要。
对 29 例临床疑似 MODY 糖尿病的儿科患者进行了 TruSight One 面板下一代测序（NGS）和多重连接依赖性探针扩增（MLPA）检测。
在这项研究中，我们在 29 例患者中的 22 例（75.9%）中发现了 MODY 基因的变异。使用两种遗传检测方法，NGS 和 MLPA，我们在患者中检测到了单核苷酸变异和大片段缺失。大多数患者携带 GCK 基因的变异（11/22），其次是 HNF1B（5/22）。其余的变异发生在 NEUROD1 和 HNF1A 基因中。我们在 GCK 基因中发现了一个新的变异：c.596T>C，p.Val199Ala。应用的遗传检测排除了两名疑似 MODY 患者的诊断，并在其他可能与患者临床表型相关的基因中发现了变异。
在我们的 MODY 患者组中，大多数变异发生在 GCK 基因，其次是 HNF1B、NEUROD1 和 HNF1A 基因。基于 NGS 和 MLPA 的联合遗传检测为疑似 MODY 糖尿病患者提供了一种全面的分析方法，并成功地对 MODY 亚型进行了鉴别诊断。
