The HNF1B score is a simple tool to select patients for HNF1B gene analysis
The HNF1B score is a simple tool to select patients for HNF1B gene analysis
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DOI：
10.1038/ki.2014.202
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发表时间：
2014-11-01
影响因子：
19.6
通讯作者：
Chauveau, Dominique
中科院分区：
文献类型：
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作者：
Faguer, Stanislas;Chassaing, Nicolas;Chauveau, Dominique
HNF1B 相关疾病是一种新出现的疾病，其特征为常染色体显性遗传、50% 的新发突变率和高度可变的表型（肾脏受累、年轻 5 型成年发病糖尿病、胰腺发育不全以及泌尿生殖道和肝脏检查异常）。鉴于目前缺乏病理特征且与其他病症广泛重叠，基因测试是诊断金标准。然而，基因前筛查是强制性的，因为基因检测的成本很高。我们的目标是根据临床、影像和生物变量开发 HNF1B 评分，作为合理基因检测的关键工具。根据已发表系列中的频率和特异性，使用最具辨别力的特征的加权组合来创建分数。 HNF1B评分根据产前发现、家族史、器官受累（肾、胰、肝、生殖道）等17项进行计算。该评分的表现是通过对包含 56 例 HNF1B 病例的 433 人队列进行 ROC 曲线分析来评估的。 HNF1B 评分有效且显着地区分突变和非突变病例（AUC 0.78）。排除疑似个体 HNF1B 突变的阴性预测值的最佳截止阈值为 8（敏感性 98.2%，特异性 41.1%，阴性预测值超过 99%）。因此，HNF1B 评分是一种简单而准确的工具，可以为选择 HNF1B 筛查患者提供更合理的方法。
HNF1B-related disease is an emerging condition characterized by an autosomal-dominant inheritance, a 50% rate of de novo mutations, and a highly variable phenotype (renal involvement, maturity-onset diabetes of the young type 5, pancreatic hypoplasia, and urogenital tract and liver test abnormalities). Given the current lack of pathognomonic characteristics and the wide overlap with other conditions, a genetic test is the diagnostic gold standard. However, pre-genetic screening is mandatory because genetic testing has substantial costs. Our aim was to develop a HNF1B score, based on clinical, imaging, and biological variables, as a pivotal tool for rational genetic testing. A score was created using a weighted combination of the most discriminative characteristics based on the frequency and specificity in published series. The HNF1B score is calculated upon 17 items including antenatal discovery, family history, and organ involvement (kidney, pancreas, liver, and genital tract). The performance of the score was assessed by a ROC curve analysis in a 433-individual cohort containing 56 HNF1B cases. The HNF1B score efficiently and significantly discriminated between mutated and nonmutated cases (AUC 0.78). The optimal cutoff threshold for the negative predictive value to rule out HNF1B mutations in a suspected individual was 8 (sensitivity 98.2%, specificity 41.1%, and negative predictive value over 99%). Thus, the HNF1B score is a simple and accurate tool to provide a more rational approach to select patients for HNF1B screening.