Laudus Nele, Audrézet Marie-Pierre, Girodon Emmanuelle, Morris Michael A, Radojkovic Dragica, Raynal Caroline, Seia Manuela, Štambergová Alexandra, Torkler Heike, Yamamoto Raina, Dequeker Elisabeth M C
Biomedical Quality Assurance Research Unit, Department of Public Health and Primary Care, University of Leuven, Leuven, Belgium.
Laboratoire de Génétique Moléculaire, CHU Brest, Brest, France.
J Cyst Fibros. 2020 Nov;19(6):969-974. doi: 10.1016/j.jcf.2020.05.005. Epub 2020 Jun 3.
The clinical spectrum associated with cystic fibrosis transmembrane conductance regulator (CFTR) variant p.Arg117His is highly variable, ranging from full-blown cystic fibrosis (CF) in a small number of cases to CFTR-related disorders (CFTR-RDs) or no symptoms at all. Therefore, taking into account phenotype variability is essential for interpretation. External quality assessment (EQA) schemes can help laboratories to objectively assess the quality of genotyping and reporting by the laboratory.
We performed a retrospective longitudinal data analysis on laboratory performance regarding the interpretation of p.Arg117His during CF EQA scheme participation. Completeness and accuracy of reporting on two mock clinical cases were each compared over time (case 1: 2005, 2007 and 2012; case 2: 2015 and 2018). These cases concerned subjects compound heterozygous for p.Phe508del and p.Arg117His in cis with 7T, but with different clinical backgrounds (family planning (case 1) versus diagnostic testing for a child (case 2)). Furthermore, we analyzed the influence of previous participations, annual test volume, accreditation status and laboratory setting on overall performance.
Overall performance improved over time, except during the 2007 CF EQA scheme. In addition, previous participations had a beneficial effect on laboratory performance. Accreditation status, annual test volume and laboratory setting did not significantly influence total interpretation scores.
In general, laboratories performed well on both cases, although reporting on the variable clinical spectrum of p.Arg117His in cis with 7T and on the disease liability of individual CFTR variants can still improve. Moreover, this study underlined the educational role of CF EQA schemes.
与囊性纤维化跨膜传导调节因子（CFTR）基因变异p.Arg117His相关的临床谱高度可变，从少数典型的囊性纤维化（CF）病例到CFTR相关疾病（CFTR-RDs），甚至完全没有症状。因此，考虑表型变异性对于解读至关重要。外部质量评估（EQA）计划可以帮助实验室客观评估基因分型和报告的质量。
我们对参与CF EQA计划期间关于p.Arg117His解读的实验室表现进行了回顾性纵向数据分析。比较了两个模拟临床病例报告的完整性和准确性随时间的变化（病例1：2005年、2007年和2012年；病例2：2015年和2018年）。这些病例涉及p.Phe508del和p.Arg117His顺式与7T复合杂合的受试者，但临床背景不同（计划生育（病例1）与儿童诊断检测（病例2））。此外，我们分析了以往参与情况、年度检测量、认可状态和实验室设置对整体表现的影响。
除2007年CF EQA计划期间外，整体表现随时间有所改善。此外，以往的参与对实验室表现有有益影响。认可状态、年度检测量和实验室设置对总解读分数没有显著影响。
总体而言，实验室在这两个病例上表现良好，尽管关于p.Arg117His顺式与7T的可变临床谱以及单个CFTR变异的疾病易感性的报告仍可改进。此外，本研究强调了CF EQA计划的教育作用。
