Department of Pathology, University of Texas Southwestern Medical Center, Dallas.
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas.
JAMA Pediatr. 2019 Jan 1;173(1):e182302. doi: 10.1001/jamapediatrics.2018.2302. Epub 2019 Jan 7.
Clinical genomic tests that examine the DNA sequence of large numbers of genes are commonly used in the diagnosis and management of epilepsy in pediatric patients. The permanence of genomic test result interpretations is not known.
To investigate the value of reinterpreting previously reported genomic test results.
DESIGN, SETTING, AND PARTICIPANTS: This study retrospectively reviewed and reinterpreted genomic test results from July 1, 2012, to August 31, 2015, for pediatric patients who previously underwent genomic epilepsy testing at a single tertiary care pediatric health care facility. Reinterpretation of previously reported variants was conducted in May 2017.
Patient reports from clinical genomic epilepsy tests were reviewed, and all reported genetic variants were reinterpreted using 2015 consensus standards and guidelines for interpreting hereditary genetic variants. Three classification tiers were used in the reinterpretation: pathogenic or likely pathogenic variant, variant of uncertain significance (VUS), or benign or likely benign variant.
A total of 309 patients had genomic epilepsy tests performed (mean [SD] age, 5.6 [0.8] years; 163 [52.8%] male), and 185 patients had a genetic variant reported. The reported variants resulted in 61 patients with and 124 patients without a genetic diagnosis (VUS variants only). On reinterpretation of all reported variants, 67 of the 185 patients (36.2%) had a change in variant classification. Of the 67 patients with a genetic variant change in interpretation, 21 (31.3%) experienced a change in diagnosis. During the 5 years of the study, 19 of 61 patients (31.1%) with a genetic diagnosis and 48 of 124 patients (38.7%) with undiagnosed conditions (VUS only) had their results reclassified. Review of genomic reports issued during the final 2 years of the study identified reclassification of variants in 4 of 16 patients (25.0%) with a pathogenic or likely pathogenic variant and 11 of 41 patients (26.8%) with a VUS.
The identified high rate of reinterpretation in this study suggests that interpretation of genomic test results has rapidly evolved during the past 5 years. These findings suggest that reinterpretation of genomic test results should be performed at least every 2 years.
临床基因组检测可检测大量基因的 DNA 序列，常用于儿科患者癫痫的诊断和治疗。基因组检测结果解释的持久性尚不清楚。
研究重新解释先前报告的基因组检测结果的价值。
设计、地点和参与者：本研究回顾性地审查和重新解释了 2012 年 7 月 1 日至 2015 年 8 月 31 日期间在一家三级儿科医疗保健机构接受过基因组癫痫检测的儿科患者的先前报告的基因组检测结果。先前报告的变异于 2017 年 5 月重新解释。
审查临床基因组癫痫检测的患者报告，使用 2015 年遗传变异解释的共识标准和指南重新解释所有报告的遗传变异。重新解释使用了三个分类层次：致病性或可能致病性变异、意义不明的变异（VUS）或良性或可能良性变异。
共对 309 例患者进行了基因组癫痫检测（平均[标准差]年龄，5.6[0.8]岁；163[52.8%]为男性），其中 185 例患者报告存在遗传变异。报告的变异导致 61 例患者有遗传诊断，124 例患者无遗传诊断（仅 VUS 变异）。重新解释所有报告的变异后，185 例患者中有 67 例（36.2%）变异分类发生变化。在 67 例变异解释发生变化的患者中，21 例（31.3%）诊断发生变化。在研究的 5 年期间，61 例有遗传诊断的患者中有 19 例（31.1%）和 124 例无诊断的患者中有 48 例（38.7%）（仅 VUS）结果重新分类。对研究最后 2 年发布的基因组报告进行审查，发现 4 例（25.0%）致病性或可能致病性变异和 11 例（26.8%）VUS 患者的变异重新分类。
本研究中发现的高重新解释率表明，在过去 5 年中，基因组检测结果的解释迅速发展。这些发现表明，基因组检测结果的重新解释应至少每 2 年进行一次。
