Department of Gynecology and Obstetrics, Division of Maternal Fetal Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA.
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD, USA.
Prenat Diagn. 2020 Apr;40(5):590-595. doi: 10.1002/pd.5650. Epub 2020 Feb 17.
We sought to evaluate the performance of exome sequencing (ES) in determining an underlying genetic etiology for cases of fetal pleural effusions.
We examined a prospective cohort series of fetal pleural effusions visualized sonographically between 1 April 2016 and 31 August 2017. Fetal pleural effusions attributed to twin sharing, anemia, or structural anomalies were excluded, as were all cases with a genetic diagnosis established by karyotype or chromosomal microarray analysis. The remaining cases with pleural effusions of unclear etiology were offered ES. ES was performed by clinical sequencing and/or sequencing under the Baylor-Hopkins Center for Mendelian Genomics' (BHCMG) research platform. All cases were evaluated for novel genes or phenotypic expansion of disease-causing genes.
ES was performed on six probands affected by pleural effusions. A pathogenic variant was identified in one case (16.7%). Four additional cases had variants of uncertain significance (VUS) in candidate genes of pathological interest. Neither clinical nor candidate genes were evident in the final case.
ES should be considered in the evaluation of prenatally detected idiopathic pleural effusions when other diagnostic workup for a genetic etiology has failed.
我们旨在评估外显子组测序（ES）在确定胎儿胸腔积液病例潜在遗传病因方面的性能。
我们研究了 2016 年 4 月 1 日至 2017 年 8 月 31 日期间超声检查发现的胎儿胸腔积液的前瞻性队列系列。排除了因双胞胎共享、贫血或结构异常导致的胸腔积液，以及通过核型或染色体微阵列分析确定遗传诊断的所有病例。对于病因不明的胸腔积液的其余病例，提供 ES 检查。ES 通过临床测序和/或 Baylor-Hopkins 孟德尔基因组学中心（BHCMG）研究平台下的测序进行。所有病例均评估了新基因或致病基因表型扩展。
对 6 名受胸腔积液影响的先证者进行了 ES 检查。在 1 例（16.7%）中发现了致病性变异。另外 4 例在有病理意义的候选基因中存在意义不明的变异（VUS）。在最后一例中，既没有临床意义，也没有候选基因。
当其他遗传病因的诊断性检查失败时，应考虑在评估产前发现的特发性胸腔积液时进行 ES。
