Division of Endocrinology, Diabetes and Metabolism, Hospital de Santo António - Centro Hospitalar e Universitário do Porto, Porto, Portugal.
Division of Pediatric Endocrinology, Department of Pediatrics, Centro Materno-Infantil do Norte - Centro Hospitalar e Universitário do Porto, Porto, Portugal.
Endocrinol Diabetes Metab. 2022 Sep;5(5):e00332. doi: 10.1002/edm2.332. Epub 2022 Jul 12.
MODY probability calculator (MPC) represents an easy-to-use tool developed by Exeter University to help clinicians prioritize which individuals should be oriented to genetic testing. We aimed to assess the utility of MPC in a Portuguese cohort with early-onset monogenic diabetes.
This single-centre retrospective study enrolled 132 participants submitted to genetic testing between 2015 and 2020. Automatic sequencing and, in case of initial negative results, generation sequencing were performed. MODY probability was calculated using the probability calculator available online. Positive and negative predictive values (PPV and NPV, respectively), accuracy, sensitivity and specificity of the calculator were determined for this cohort.
Seventy-three individuals were included according to inclusion criteria: 20 glucokinase (GCK-MODY); 16 hepatocyte nuclear factor 1A (HNF1A-MODY); 2 hepatocyte nuclear factor 4A (HNF4A-MODY) and 35 DM individuals with no monogenic mutations found. The median probability score of MODY was significantly higher in monogenic diabetes-positive subgroup (75.5% vs. 24.2%, p < .001). The discriminative accuracy of the calculator, as expressed by area under the curve, was 75% (95% CI: 64%-85%). In our cohort, the best cut-off value for the MODY calculator was found to be 36%, with a PPV of 74.4%, NPV of 73.5% and corresponding sensitivity and specificity of 76.2% and 71.4%, respectively.
In a highly pre-selected group of probands qualified for genetic testing, the Exeter MODY probability calculator provided a useful tool in individuals' selection for genetic testing, with good discrimination ability under an optimal probability cut-off of 36%. Further geographical and population adjustments are warranted for general use.
MODY 概率计算器（MPC）是由埃克塞特大学开发的一种易于使用的工具，旨在帮助临床医生确定哪些个体应进行基因检测。本研究旨在评估 MPC 在葡萄牙早发性单基因糖尿病患者中的应用价值。
本单中心回顾性研究纳入了 2015 年至 2020 年期间接受基因检测的 132 名参与者。我们进行了自动测序，并且在初始结果阴性的情况下进行了生成测序。使用在线计算器计算 MODY 概率。我们确定了该队列计算器的阳性和阴性预测值（PPV 和 NPV）、准确性、敏感性和特异性。
根据纳入标准，有 73 名患者纳入本研究：20 名葡萄糖激酶（GCK-MODY）患者、16 名肝细胞核因子 1A（HNF1A-MODY）患者、2 名肝细胞核因子 4A（HNF4A-MODY）患者和 35 名未发现单基因突变的糖尿病患者。单基因糖尿病阳性亚组的 MODY 概率中位数明显更高（75.5%比 24.2%，p<0.001）。曲线下面积（AUC）表示计算器的判别准确性为 75%（95%CI：64%-85%）。在本队列中，MODY 计算器的最佳截断值为 36%，PPV 为 74.4%，NPV 为 73.5%，相应的敏感性和特异性分别为 76.2%和 71.4%。
在经过高度选择的适合进行基因检测的先证者群体中，埃克塞特 MODY 概率计算器为个体选择基因检测提供了有用的工具，在最佳概率截断值 36%下具有良好的判别能力。需要进行进一步的地理和人群调整，以使其得到更广泛的应用。
