Unit of Diagnosis and Treatment of Congenital Metabolic Diseases, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain.
Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain.
Orphanet J Rare Dis. 2022 Mar 4;17(1):105. doi: 10.1186/s13023-022-02263-3.
Diagnosis of mature-onset diabetes of the young (MODY), a non-autoimmune monogenic form of diabetes mellitus, is confirmed by genetic testing. However, a positive genetic diagnosis is achieved in only around 50% of patients with clinical characteristics of this disease.
We evaluated the diagnostic utility of transcriptomic analysis in patients with clinical suspicion of MODY but a negative genetic diagnosis. Using Nanostring nCounter technology, we conducted transcriptomic analysis of 19 MODY-associated genes in peripheral blood samples from 19 patients and 8 healthy controls. Normalized gene expression was compared between patients and controls and correlated with each patient's biochemical and clinical variables. Z-scores were calculated to identify significant changes in gene expression in patients versus controls. Only 7 of the genes analyzed were detected in peripheral blood. HADH expression was significantly lower in patients versus controls. Among patients with suspected MODY, GLIS3 expression was higher in obese versus normal-weight patients, and in patients aged < 25 versus > 25 years at diabetes onset. Significant alteration with respect to controls of any gene was observed in 57.9% of patients.
Although blood does not seem to be a suitable sample for transcriptomic analysis of patients with suspected MODY, in our study, we detected expression alterations in some of the genes studied in almost 58% of patients. That opens the door for future studies that can clarify the molecular cause of the clinic of these patients and thus be able to maintain a more specific follow-up and treatment in each case.
成熟型青年发病型糖尿病（MODY）是一种非自身免疫性单基因糖尿病，其诊断通过基因检测确认。然而，具有这种疾病临床特征的患者中，仅有约 50%能通过遗传诊断确诊。
我们评估了转录组分析在临床疑似 MODY 但基因诊断阴性的患者中的诊断效用。我们使用 Nanostring nCounter 技术对 19 名患者和 8 名健康对照者的外周血样本进行了 19 个与 MODY 相关的基因的转录组分析。比较了患者和对照者的标准化基因表达，并与每位患者的生化和临床变量相关联。计算 Z 分数以确定患者与对照者之间基因表达的显著变化。分析的仅 7 个基因在外周血中被检测到。与对照者相比，患者的 HADH 表达明显更低。在疑似 MODY 的患者中，与体重正常者相比，肥胖患者的 GLIS3 表达更高，且发病年龄<25 岁的患者与发病年龄>25 岁的患者相比，GLIS3 表达更高。与对照者相比，57.9%的患者有任何基因的显著改变。
尽管血液似乎不是疑似 MODY 患者转录组分析的合适样本，但在我们的研究中，我们在近 58%的患者中检测到一些研究基因的表达改变。这为未来的研究打开了大门，未来的研究可以阐明这些患者临床表现的分子原因，从而能够在每个病例中进行更具针对性的随访和治疗。
