1] Département de Néphrologie et Transplantation d'organes, Hôpital Rangueil, CHU Toulouse, France [2] Centre de référence des maladies rénales rares, Toulouse, France [3] Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Institute of Cardiovascular and Metabolic Disease, Toulouse, France [4] Université Toulouse III Paul-Sabatier, Toulouse, France.
1] Université Toulouse III Paul-Sabatier, Toulouse, France [2] Service de Génétique médicale et UPS III EA4555, Hôpital Purpan, CHU de Toulouse, France.
Kidney Int. 2014 Nov;86(5):1007-15. doi: 10.1038/ki.2014.202. Epub 2014 Jun 4.
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.
HNF1B 相关疾病是一种新兴病症，具有常染色体显性遗传、50%的新生突变率和高度可变的表型（肾脏受累、成年起病的 5 型糖尿病、胰腺发育不良以及泌尿生殖系统和肝脏检查异常）等特征。鉴于目前缺乏特征性表现，且与其他病症存在广泛重叠，基因检测是诊断的金标准。但是，在进行基因检测之前必须进行预基因筛查，因为基因检测的费用很高。我们的目标是基于临床、影像学和生物学变量，开发一种 HNF1B 评分，作为合理进行基因检测的重要工具。该评分是根据发表的系列研究中频率和特异性最高的鉴别特征，通过加权组合来创建的。HNF1B 评分通过 17 项指标计算得出，包括产前发现、家族史和器官受累（肾脏、胰腺、肝脏和生殖系统）。我们在包含 56 例 HNF1B 病例的 433 例个体队列中，通过 ROC 曲线分析评估了评分的性能。HNF1B 评分能够有效且显著地区分突变和非突变病例（AUC 为 0.78）。在疑似个体中，排除 HNF1B 突变的阴性预测值的最佳截断阈值为 8（敏感性为 98.2%，特异性为 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，可提供一种更合理的方法来选择需要进行 HNF1B 筛查的患者。
