Clinic for Paediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany.
Biomedical Research in Endstage and Obstructive Lung Disease (BREATH), German Center for Lung Research DZL, Hannover, Germany.
BMJ Open Respir Res. 2020 Oct;7(1). doi: 10.1136/bmjresp-2020-000736.
Nasal potential difference (NPD) and intestinal current measurements (ICM) are cystic fibrosis transmembrane conductance regulator (CFTR) biomarkers recommended to make a diagnosis in individuals with inconclusive sweat test and genetics and a clinical suspicion for cystic fibrosis (CF) or CFTR-related disorder (CFTR-RD).
NPD and ICM were measured according to standard operating procedures of the European Cystic Fibrosis Society Diagnostic Network Working Group.
We assessed 219 individuals by NPD or ICM who had been referred to our laboratory due to clinical symptoms suggestive of CF, but inconclusive sweat test and genetics (median age: 16.3 years, range 0.4 to 76 years). CF or CFTR-related disorder was diagnosed in 22 of 29 patients (76%) with a genotype of unknown or variable clinical significance and in 51 of 190 carriers (27%) of one (35/42) or no (16/148) identified mutation. If two sequence variants had been identified, the outcome of NPD and ICM was consistent with the classification of the CFTR2 database. Moreover, a suspected false-positive diagnosis of CF was confirmed in seven and withdrawn in eight patients. Of 26 individuals assessed by both NPD and ICM, eleven individuals exhibited discordant tracings of ICM and NPD, with one measurement being in the CF range and the other in the normal range.
The majority of patients whom we diagnosed with CF or CFTR-RD by extended electrophysiology are carriers of the wild-type coding sequence on at least one of their CF alleles. The disease-causing genetic lesions should reside in the non-coding region of or elsewhere in the genome, affecting the regulation of CFTR expression in a tissue-depending fashion which may explain the large within-group variability of CFTR activity in the respiratory and intestinal epithelium seen in this group.
鼻电位差（NPD）和肠道电流测量（ICM）是囊性纤维化跨膜电导调节剂（CFTR）生物标志物，建议用于在汗液试验结果不确定且具有遗传背景和临床疑似囊性纤维化（CF）或 CFTR 相关疾病（CFTR-RD）的个体中进行诊断。
按照欧洲囊性纤维化协会诊断网络工作组的标准操作程序测量 NPD 和 ICM。
我们评估了 219 名因具有 CF 临床症状但汗液试验和遗传学结果不确定的个体，这些个体被转诊到我们的实验室（中位年龄 16.3 岁，范围 0.4 至 76 岁）。在具有未知或可变临床意义的基因型的 29 名患者中的 22 名（76%）和在 190 名携带者（27%）中的 51 名（35/42）或无（16/148）鉴定出 1 个突变的患者中诊断为 CF 或 CFTR-RD。如果鉴定出两个 序列变异，则 NPD 和 ICM 的结果与 CFTR2 数据库的分类一致。此外，在 7 名患者中确认了疑似 CF 的假阳性诊断，并在 8 名患者中撤回了该诊断。在通过扩展电生理学评估的 26 名个体中，11 名个体的 ICM 和 NPD 记录不一致，一项测量结果处于 CF 范围，另一项测量结果处于正常范围。
我们通过扩展电生理学诊断为 CF 或 CFTR-RD 的大多数患者至少在其 CF 等位基因的一个上携带野生型 编码序列。致病的遗传病变应位于 非编码区域或基因组的其他部位，以组织依赖性方式影响 CFTR 表达的调节，这可以解释在该组中观察到的呼吸道和肠道上皮 CFTR 活性的较大组内变异性。
