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Genomic autopsy to identify underlying causes of pregnancy loss and perinatal death

2023; Nature Portfolio; Volume: 29; Issue: 1 Linguagem: Inglês

10.1038/s41591-022-02142-1

1546-170X

Alicia B. Byrne, Peer Arts, Thuong Ha, Karin S. Kassahn, Lynn Pais, Anne O’Donnell‐Luria, François Aguet, Harindra Arachchi, Christina Austin‐Tse, Lawrence Babb, Samantha Baxter, Harrison Brand, Jaime Chang, Katherine R. Chao, Ryan L. Collins, Beryl B. Cummings, Kayla Delano, Stephanie DiTroia, Eleina England, Emily Evangelista, Selin Everett, Laurent C. Francioli, Jack B. Fu, Vijay Ganesh, Kiran Garimella, Laura D. Gauthier, Julia K. Goodrich, Sanna Gudmundsson, Stacey J. Hall, Yongqing Huang, Steve Jahl, Kristen M. Laricchia, Kathryn E. Larkin, Monkol Lek, Gabrielle Lemire, Rachel B. Lipson, Alysia Kern Lovgren, Daniel G. MacArthur, Brian Mangilog, Stacy Mano, Jamie L. Marshall, Thomas E. Mullen, Kevin K. Nguyen, Emily O’Heir, Melanie O’Leary, Ikeoluwa Osei‐Owusu, Jorge Perez de Acha Chavez, Emma Pierce‐Hoffman, Heidi L. Rehm, Jillian Serrano, Moriel Singer‐Berk, Hana Snow, Matthew Solomonson, Rachel G. Son, Abigail Sveden, Michael E. Talkowski, Grace Tiao, Miriam S. Udler, Zaheer Valivullah, Elise Valkanas, Grace E. VanNoy, Qingbo Wang, Nicholas A. Watts, Ben Weisburd, Clara E. Williamson, Michael W. Wilson, Lauren Witzgall, Monica H. Wojcik, Isaac Wong, Jordan C. Wood, Shifa Zhang, Milena Babic, Mahalia S. B. Frank, Jinghua Feng, Paul Wang, David Lawrence, Leila Eshraghi, Luis Arriola, John Toubia, Van Hung Nguyen, Disna Abeysuriya, Lesley C. Adès, David J. Amor, Susan Arbuckle, Madhura Bakshi, Bligh Berry, Tiffany Boughtwood, Adam Bournazos, Alessandra Bray, Fiona Chan, Yuen Chan, Clara W. T. Chung, Jonathan R. Clark, Jackie Collett, Alison Colley, Felicity Collins, Sandra T. Cooper, Mark Corbett, Jane E. Dahlstrom, Peter A. Dargaville, Janene Davies, Tenielle Davis, Jarrad Dearman, Jayanthi Dissanayake, Julia Dobbins, Helen Doyle, Andrew Dubowsky, Matthew Edwards, Lisa Ewans, Mitali Fadia, Andrew Fennell, Keri Finlay, Andrew S. French, Kathryn Friend, Alison Gardner, Jozef Gécz, Nicole Graf, Eric Haan, Georgina Hollingsworth, Ari Horton, Denise Howting, Matthew F. Hunter, Gareth Jevon, Benjamin Kamien, Debra Kennedy, T. Yee Khong, Michael Krivanek, Thessa Kroes, Emma Krzesinski, Edward Kwan, Stephanie Lau, Shannon LeBlanc, Jan Liebelt, Suzanna Lindsey-Temple, Jill Lipsett, Christine Loo, Julia Low, Amali Mallawaarachchi, Nick Manton, Admire Matsika, Tessa Mattiske, Julie McGaughran, Lesley McGregor, Namita Mittal, Ali Moghimi, Lynette Moore, Hatice Mutlu Albayrak, Jessica M.Y. Ng, Jillian Nicholl, Nicholas Pachter, J. M. Papadimitriou, Renae Parker, Sarah Parsons, Chirag Patel, Rhonda Pawlowski, Luís A. Pérez-Jurado, Jason Pinner, Katerina Politis, Cathryn Poulton, Theresa Power, Michael C. Quinn, Sulekha Rajagopalan, Matthew Regan, Jonathan Rodgers, Steuart Rorke, Rani Sachdev, Suzanne C.E.H. Sallevelt, Sarah A. Sandaradura, Maryam Shamassi, Roshan Shamon, Isabella Sherburn, Jennie Slee, Annalisa Solinas, Ella Sugo, Elizabeth D. Thompson, Sagarika Tripathy, Anand Vasudevan, M. Diaz Vazquez, Kunal Verma, Mthulisi Viki, Mathew Wallis, Dani L. Webber, Martin Weber, Karen Whale, Meredith Wilson, Lisa Worgan, Yu Sui, George McGillivray, Jason Pinner, F. Ellis McKenzie, Rebecca Morrow, Jill Lipsett, Nick Manton, T. Yee Khong, Lynette Moore, Jan Liebelt, Andreas Schreiber, Sarah L. King‐Smith, Tristan Hardy, Matilda R. Jackson, Christopher Barnett, Hamish S. Scott,

Ethics and Legal Issues in Pediatric Healthcare

Abstract Pregnancy loss and perinatal death are devastating events for families. We assessed ‘genomic autopsy’ as an adjunct to standard autopsy for 200 families who had experienced fetal or newborn death, providing a definitive or candidate genetic diagnosis in 105 families. Our cohort provides evidence of severe atypical in utero presentations of known genetic disorders and identifies novel phenotypes and disease genes. Inheritance of 42% of definitive diagnoses were either autosomal recessive (30.8%), X-linked recessive (3.8%) or autosomal dominant (excluding de novos, 7.7%), with risk of recurrence in future pregnancies. We report that at least ten families (5%) used their diagnosis for preimplantation (5) or prenatal diagnosis (5) of 12 pregnancies. We emphasize the clinical importance of genomic investigations of pregnancy loss and perinatal death, with short turnaround times for diagnostic reporting and followed by systematic research follow-up investigations. This approach has the potential to enable accurate counseling for future pregnancies.