Neeta L Vora1, Kelly Gilmore2, Alicia Brandt3, Chelsea Gustafson3, Natasha Strande3,4, Lori Ramkissoon3,4, Emily Hardisty2, Ann Katherine M Foreman3, Kirk Wilhelmsen5, Phillips Owen6, Karen E Weck3,4, Jonathan S Berg3, Cynthia M Powell3,7, Bradford C Powell3. 1. Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. neeta_vora@med.unc.edu. 2. Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. 3. Department of Genetics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. 4. Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. 5. Departments of Genetics and Neurology, Renaissance Computing Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. 6. Renaissance Computing Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. 7. Department of Pediatrics, Division of Genetics and Metabolism, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Abstract
PURPOSE: We investigated the diagnostic and clinical performance of trio exome sequencing (ES) in parent-fetus trios where the fetus had sonographic abnormalities but normal karyotype, microarray and, in some cases, normal gene-specific sequencing. METHODS: ES was performed from DNA of 102 anomalous fetuses and from peripheral blood from their parents. Parents provided consent for the return of diagnostic results in the fetus, medically actionable findings in the parents, and identification as carrier couple for significant autosomal recessive conditions. RESULTS: In 21/102 (20.6%) fetuses, ES provided a positive-definitive or positive-probable diagnosis. In 10/102 (9.8%), ES provided an inconclusive-possible result. At least 2/102 (2.0%) had a repeat pregnancy during the study period and used the information from the study for prenatal diagnosis in the next pregnancy. Six of 204 (2.9%) parents received medically actionable results that affected their own health and 3/102 (2.9%) of couples received results that they were carriers for the same autosomal recessive condition. CONCLUSION: ES has diagnostic utility in a select population of fetuses where a genetic diagnosis was highly suspected. Challenges related to genetics literacy, variant interpretation, and various types of diagnostic results affecting both fetal and parental health must be addressed by highly tailored pre- and post-test genetic counseling.
PURPOSE: We investigated the diagnostic and clinical performance of trio exome sequencing (ES) in parent-fetus trios where the fetus had sonographic abnormalities but normal karyotype, microarray and, in some cases, normal gene-specific sequencing. METHODS: ES was performed from DNA of 102 anomalous fetuses and from peripheral blood from their parents. Parents provided consent for the return of diagnostic results in the fetus, medically actionable findings in the parents, and identification as carrier couple for significant autosomal recessive conditions. RESULTS: In 21/102 (20.6%) fetuses, ES provided a positive-definitive or positive-probable diagnosis. In 10/102 (9.8%), ES provided an inconclusive-possible result. At least 2/102 (2.0%) had a repeat pregnancy during the study period and used the information from the study for prenatal diagnosis in the next pregnancy. Six of 204 (2.9%) parents received medically actionable results that affected their own health and 3/102 (2.9%) of couples received results that they were carriers for the same autosomal recessive condition. CONCLUSION: ES has diagnostic utility in a select population of fetuses where a genetic diagnosis was highly suspected. Challenges related to genetics literacy, variant interpretation, and various types of diagnostic results affecting both fetal and parental health must be addressed by highly tailored pre- and post-test genetic counseling.
Authors: Kate Swanson; Mary E Norton; Billie R Lianoglou; Angie C Jelin; Ugur Hodoglugil; Jessica Van Ziffle; Patrick Devine; Teresa N Sparks Journal: Prenat Diagn Date: 2022-07-03 Impact factor: 3.242
Authors: Asha N Talati; Kelly L Gilmore; Emily E Hardisty; Anne D Lyerly; Christine Rini; Neeta L Vora Journal: Prenat Diagn Date: 2022-02-16 Impact factor: 3.242
Authors: Melissa Hill; Sian Ellard; Jane Fisher; Naomi Fulop; Marian Knight; Mark Kroese; Jean Ledger; Kerry Leeson-Beevers; Alec McEwan; Dominic McMullan; Rhiannon Mellis; Stephen Morris; Michael Parker; Dagmar Tapon; Emma Baple; Laura Blackburn; Asya Choudry; Caroline Lafarge; Hannah McInnes-Dean; Michelle Peter; Rema Ramakrishnan; Lauren Roberts; Beverly Searle; Emma Smith; Holly Walton; Sarah L Wynn; Wing Han Wu; Lyn S Chitty Journal: NIHR Open Res Date: 2022-07-18
Authors: Kate Swanson; Teresa N Sparks; Billie R Lianoglou; Flavia Chen; Sarah Downum; Sachi Patel; Shannon Rego; Tiffany Yip; Jessica Van Ziffle; Barbara A Koenig; Anne M Slavotinek; Mary E Norton Journal: Prenat Diagn Date: 2021-06-07 Impact factor: 3.242