Angie C Jelin1,2, Nara Sobreira2,3, Elizabeth Wohler2,3, Benjamin Solomon4, Teresa Sparks5, Katelynn G Sagaser1, Katherine R Forster6, Jena Miller6, P Dane Witmer2,3, Ada Hamosh2,3, David Valle2,3, Karin Blakemore1,2. 1. Department of Gynecology and Obstetrics, Division of Maternal Fetal Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA. 2. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD, USA. 3. Baylor-Hopkins Center for Mendelian Genomics, Baltimore, MD, USA. 4. GeneDx, Bethesda, MD, USA. 5. Department of Obstetrics, Gynecology & Reproductive Sciences, Division of Maternal Fetal Medicine, University of California, San Francisco, CA, USA. 6. Department of Gynecology and Obstetrics, Center for Fetal Therapy, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Abstract
OBJECTIVE: We sought to evaluate the performance of exome sequencing (ES) in determining an underlying genetic etiology for cases of fetal pleural effusions. STUDY DESIGN: 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. RESULTS: 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. CONCLUSION: ES should be considered in the evaluation of prenatally detected idiopathic pleural effusions when other diagnostic workup for a genetic etiology has failed.
OBJECTIVE: We sought to evaluate the performance of exome sequencing (ES) in determining an underlying genetic etiology for cases of fetal pleural effusions. STUDY DESIGN: 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. RESULTS: 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. CONCLUSION: ES should be considered in the evaluation of prenatally detected idiopathic pleural effusions when other diagnostic workup for a genetic etiology has failed.
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