Assessment of the HNF1B Score as a Tool to Select Patients for HNF1B Genetic Testing.
Assessment of the HNF1B Score as a Tool to Select Patients for HNF1B Genetic Testing.
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作者：
Clissold R;Shields B;Ellard S;Hattersley A;Bingham C
肝细胞核因子1 β（HNF 1B）相关疾病的诊断是一项具有挑战性的任务，由于表型的变异性和经常缺乏家族史。最近开发了HNF1B评分，以帮助选择合适的患者进行基因检测，阴性预测值（NPV）为99%。我们的目的是在大量转介HNF1B基因检测到英国HNF1B基因诊断检测服务中测试该评分的临床实用性。使用转诊时提供的临床信息，为686名英国转介的HNF1B基因检测人员分配了HNF1B评分。通过受试者工作特征曲线分析评价评分的性能。不同临床特征对HNF1B相关疾病基因诊断的相对区分能力仅在英国数据集中进行了估计，并与法国数据合并。HNF1B评分可以很好地区分有突变和无突变的患者，曲线下面积为0.72。应用建议的临界评分≥ 8，得出的NPV为85%。在一项汇总分析中，产前肾脏异常、肾强回声性和囊肿在儿童中具有歧视性，而肾发育不全和囊肿在成人中具有歧视性。胰腺异常是歧视性的，而其他肾外的特点有一个大的影响大小，只有在成人。HNF1B评分在一个单一的英国中心测试的一个大型队列中对HNF1B突变具有歧视性。较低的NPV（85%对99%）降低了其在选择HNF1B基因检测患者时的临床实用性，尽管需要在前瞻性队列中进行验证。
Diagnosing hepatocyte nuclear factor 1β (HNF1B)-related disease is a challenging task due to the phenotypic variability and frequent absence of a family history. An HNF1B score has recently been developed to help select appropriate patients for genetic testing with a negative predictive value (NPV) of 99%. We aimed at testing the clinical utility of this score in a large number of referrals for HNF1B genetic testing to the UK diagnostic testing service for the HNF1B gene. An HNF1B score was assigned for 686 UK referrals for HNF1B genetic testing using clinical information available at referral. The performance of the score was evaluated by receiver-operating characteristic curve analysis. The relative discriminatory ability of different clinical features for making a genetic diagnosis of HNF1B-related disease were estimated in the UK dataset alone and pooled with French data. The HNF1B score discriminated between patients with and without a mutation reasonably well with an area under the curve of 0.72. Applying the suggested cut-off score of ≥8 gave a NPV of 85%. In a pooled analysis, antenatal renal abnormalities, renal hyperechogenicity and cysts were discriminatory in children, whereas renal hypoplasia and cysts were discriminatory in adults. Pancreatic abnormalities were discriminatory in both, whereas other extra-renal characteristics had a large effect size only in adults. The HNF1B score was discriminatory for HNF1B mutations in a large cohort of individuals tested in a single UK centre. The lower NPV (85 vs. 99%) reduces its clinical utility in selecting patients for HNF1B genetic testing, although validation in a prospective cohort is required.