Genomic autopsy to identify underlying causes of pregnancy loss and perinatal death
Authors: Byrne Alicia B. , Arts Peer , Ha Thuong T. , Kassahn Karin S. , Pais Lynn S. , O’Donnell-Luria Anne ,   Broad Institute Center for Mendelian Genomics, Aguet François , Arachchi Harindra M. , Austin-Tse Christina A. , Babb Larry , Baxter Samantha M. , Brand Harrison , Chang Jaime , Chao Katherine R. , Collins Ryan L. , Cummings Beryl , Delano Kayla , DiTroia Stephanie P. , England Eleina , Evangelista Emily , Everett Selin , Francioli Laurent C. , Fu Jack , Ganesh Vijay S. , Garimella Kiran V. , Gauthier Laura D. , Goodrich Julia K. , Gudmundsson Sanna , Hall Stacey J. , Huang Yongqing , Jahl Steve , Laricchia Kristen M. , Larkin Kathryn E. , Lek Monkol , Lemire Gabrielle , Lipson Rachel B. , Lovgren Alysia Kern , MacArthur Daniel G. , Mangilog Brian E. , Mano Stacy , Marshall Jamie L. , Mullen Thomas E. , Nguyen Kevin K. , O’Heir Emily , O’Leary Melanie C. , Osei-Owusu Ikeoluwa A. , de Acha Chavez Jorge Perez , Pierce-Hoffman Emma , Rehm Heidi L. , Serrano Jillian , Singer-Berk Moriel , Snow Hana , Solomonson Matthew , Son Rachel G. , Sveden Abigail , Talkowski Michael , Tiao Grace , Udler Miriam S. , Valivullah Zaheer , Valkanas Elise , VanNoy Grace E. , Wang Qingbo S. , Watts Nicholas A. , Weisburd Ben , Williamson Clara E. , Wilson Michael W. , Witzgall Lauren , Wojcik Monica H. , Wong Isaac , Wood Jordan C. , Zhang Shifa , Babic Milena , Frank Mahalia S. B. , Feng Jinghua , Wang Paul , Lawrence David M. , Eshraghi Leila , Arriola Luis , Toubia John , Nguyen Hung ,   Genomic Autopsy Study Research Network, Abeysuriya Disna , Ades Lesley C. , Amor David J. , Arbuckle Susan , Bakshi Madhura , Berry Bligh , Boughtwood Tiffany , Bournazos Adam , Bray Alessandra , Chan Fiona , Chan Yuen , Chung Clara , Clark Jonathan , Collett Jackie , Colley Alison , Collins Felicity , Cooper Sandra , Corbett Mark A. , Dahlstrom Jane E. , Dargaville Peter , Davies Janene , Davis Tenielle , Dearman Jarrad , Dissanayake Jayanthi , Dobbins Julia , Doyle Helen , Dubowsky Andrew , Edwards Matt , Ewans Lisa J. , Fadia Mitali , Fennell Andrew , Finlay Keri , French Andrew , Friend Kathryn , Gardner Alison E. , Gecz Jozef , Graf Nicole , Haan Eric A. , Hollingsworth Georgina , Horton Ari E. , Howting Denise , Hunter Matthew F. , Jevon Gareth , Kamien Benjamin , Kennedy Debra , Khong T. Yee , Krivanek Michael , Kroes Thessa , Krzesinski Emma I. , Kwan Edward , Lau Stephanie , LeBlanc Shannon , Liebelt Jan , Lindsey-Temple Suzanna , Lipsett Jill , Loo Christine K. C. , Low Julia , Mallawaarachchi Amali , Manton Nick , Matsika Admire , Mattiske Tessa , McGaughran Julie , McGregor Lesley , Mittal Namita , Moghimi Ali , Moore Lynette , Albayrak Hatice Mutlu , Ng Jessica , Nicholl Jillian , Pachter Nicholas , Papadimitriou John , Parker Renae , Parsons Sarah , Patel Chirag , Pawlowski Rhonda , Perez-Jurado Luis A. , Pinner Jason R. , Politis Katerina , Poulton Cathryn , Power Theresa , Quinn Michael , Rajagopalan Sulekha , Regan Matthew , Rodgers Jonathan , Rorke Steuart , Sachdev Rani , Sallevelt Suzanne , Sandaradura Sarah A. , Shamassi Maryam , Shamon Roshan , Sherburn Isabella , Slee Jennie , Solinas Annalisa , Sugo Ella , Thompson Elizabeth , Tripathy Sagarika , Vasudevan Anand , Vazquez Melisa , Verma Kunal , Viki Mthulisi , Wallis Mathew , Webber Dani L. , Weber Martin , Whale Karen , Wilson Meredith , Worgan Lisa , Yu Sui , McGillivray George , Pinner Jason , McKenzie Fiona , Morrow Rebecca , Lipsett Jill , Manton Nick , Khong T. Yee , Moore Lynette , Liebelt Jan E. , Schreiber Andreas W. , King-Smith Sarah L. , Hardy Tristan S. E. , Jackson Matilda R. , Barnett Christopher P. , Scott Hamish S. 
Published: January 2023

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.