Nathalie Brison1,2, Jazz Storms2,3, Darine Villela2, Kristl G Claeys4,5, Luc Dehaspe1,2, Thomy de Ravel1,2, Liesbeth De Waele6,7, Nathalie Goemans6, Eric Legius1,2, Hilde Peeters1,2, Hilde Van Esch1,2, Valerie Race1,2, Joris Robert Vermeesch1,2, Koenraad Devriendt1,2, Kris Van Den Bogaert8,9. 1. Center for Human Genetics, University Hospitals Leuven, Leuven, Belgium. 2. Department of Human Genetics, KU Leuven, Leuven, Belgium. 3. Faculty of Medicine, KU Leuven, Leuven, Belgium. 4. Department of Neurology, University Hospitals Leuven, Leuven, Belgium. 5. Laboratory for Muscle Diseases and Neuropathies, Department of Neurosciences, KU Leuven, Leuven, Belgium. 6. Department of Pediatric Neurology, University Hospitals Leuven, Leuven, Belgium. 7. Department of Development and Regeneration, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium. 8. Center for Human Genetics, University Hospitals Leuven, Leuven, Belgium. kris.vandenbogaert@uzleuven.be. 9. Department of Human Genetics, KU Leuven, Leuven, Belgium. kris.vandenbogaert@uzleuven.be.
Abstract
PURPOSE: Noninvasive prenatal screening (NIPS) using genome sequencing also reveals maternal copy-number variations (CNVs). Those CNVs can be clinically actionable or harmful to the fetus if inherited. CNVs in the DMD gene potentially causing dystrophinopathies are among the most commonly observed maternal CNVs. We present our experience with maternal DMD gene CNVs detected by NIPS. METHODS: We analyzed the data of maternal CNVs detected in the DMD gene revealed by NIPS. RESULTS: Of 26,123 NIPS analyses, 16 maternal CNVs in the DMD gene were detected (1/1632 pregnant women). Variant classification regarding pathogenicity and phenotypic severity was based on public databases, segregation analysis in the family, and prediction of the effect on the reading frame. Ten CNVs were classified as pathogenic, four as benign, and two remained unclassified. CONCLUSION: NIPS leverages CNV screening in the general population of pregnant women. We implemented a strategy for the interpretation and the return of maternal CNVs in the DMD gene detected by NIPS.
PURPOSE: Noninvasive prenatal screening (NIPS) using genome sequencing also reveals maternal copy-number variations (CNVs). Those CNVs can be clinically actionable or harmful to the fetus if inherited. CNVs in the DMD gene potentially causing dystrophinopathies are among the most commonly observed maternal CNVs. We present our experience with maternal DMD gene CNVs detected by NIPS. METHODS: We analyzed the data of maternal CNVs detected in the DMD gene revealed by NIPS. RESULTS: Of 26,123 NIPS analyses, 16 maternal CNVs in the DMD gene were detected (1/1632 pregnant women). Variant classification regarding pathogenicity and phenotypic severity was based on public databases, segregation analysis in the family, and prediction of the effect on the reading frame. Ten CNVs were classified as pathogenic, four as benign, and two remained unclassified. CONCLUSION: NIPS leverages CNV screening in the general population of pregnant women. We implemented a strategy for the interpretation and the return of maternal CNVs in the DMD gene detected by NIPS.