Christina L Alamillo1, Zöe Powis1, Kelly Farwell1, Layla Shahmirzadi1, Elaine C Weltmer1, John Turocy2, Thomas Lowe3, Christine Kobelka4, Emily Chen4, Donald Basel5, Elena Ashkinadze6, Lisa D'Augelli7, Elizabeth Chao1,8, Sha Tang1. 1. Ambry Genetics, Aliso Viejo, CA, USA. 2. Genetics Department, Kaiser Permanente, Clovis, CA, USA. 3. Thomas Lowe, MD, Private Practice, Boca Raton, FL, USA. 4. Genetics Department, Kaiser Permanente, San Francisco, CA, USA. 5. Division of Genetics, Medical College of Wisconsin, Milwaukee, WI, USA. 6. Division of Maternal-Fetal Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA. 7. Integrated Genetics, Westborough, MA, USA. 8. Department of Pediatrics, University of California Irvine, Irvine, CA, USA.
Abstract
OBJECTIVE: Exome sequencing is a successful option for diagnosing individuals with previously uncharacterized genetic conditions, however little has been reported regarding its utility in a prenatal setting. The goal of this study is to describe the results from a cohort of fetuses for which exome sequencing was performed. METHODS: We performed a retrospective analysis of the first seven cases referred to our laboratory for exome sequencing following fetal demise or termination of pregnancy. All seven pregnancies had multiple congenital anomalies identified by level II ultrasound. Exome sequencing was performed on trios using cultured amniocytes or products of conception from the affected fetuses. RESULTS: Relevant alterations were identified in more than half of the cases (4/7). Three of the four were categorized as 'positive' results, and one of the four was categorized as a 'likely positive' result. The provided diagnoses included osteogenesis imperfecta II (COL1A2), glycogen storage disease IV (GBE1), oral-facial-digital syndrome 1 (OFD1), and RAPSN-associated fetal akinesia deformation sequence. CONCLUSION: This data suggests that exome sequencing is likely to be a valuable diagnostic testing option for pregnancies with multiple congenital anomalies detected by prenatal ultrasound; however, additional studies with larger cohorts of affected pregnancies are necessary to confirm these findings.
OBJECTIVE: Exome sequencing is a successful option for diagnosing individuals with previously uncharacterized genetic conditions, however little has been reported regarding its utility in a prenatal setting. The goal of this study is to describe the results from a cohort of fetuses for which exome sequencing was performed. METHODS: We performed a retrospective analysis of the first seven cases referred to our laboratory for exome sequencing following fetal demise or termination of pregnancy. All seven pregnancies had multiple congenital anomalies identified by level II ultrasound. Exome sequencing was performed on trios using cultured amniocytes or products of conception from the affected fetuses. RESULTS: Relevant alterations were identified in more than half of the cases (4/7). Three of the four were categorized as 'positive' results, and one of the four was categorized as a 'likely positive' result. The provided diagnoses included osteogenesis imperfecta II (COL1A2), glycogen storage disease IV (GBE1), oral-facial-digital syndrome 1 (OFD1), and RAPSN-associated fetal akinesia deformation sequence. CONCLUSION: This data suggests that exome sequencing is likely to be a valuable diagnostic testing option for pregnancies with multiple congenital anomalies detected by prenatal ultrasound; however, additional studies with larger cohorts of affected pregnancies are necessary to confirm these findings.
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: Sunayna Best; Karen Wou; Neeta Vora; Ignatia B Van der Veyver; Ronald Wapner; Lyn S Chitty Journal: Prenat Diagn Date: 2017-07-25 Impact factor: 3.050