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

Alicia B. Byrne, Peer Arts, Thuong T. Ha, Karin S. Kassahn, Lynn S. Pais, Anne O’Donnell-Luria, Broad Institute Center for Mendelian Genomics, Milena Babic, Mahalia S.B. Frank, Jinghua Feng, Paul Wang, David M. Lawrence, Leila Eshraghi, Luis Arriola, John Toubia, Hung Nguyen, Genomic Autopsy Study Research Network, Andrew Dubowsky, Eric A. Haan, Chirag PatelGeorge McGillivray, Jason Pinner, Fiona McKenzie, Rebecca Morrow, Jill Lipsett, Nick Manton, T. Yee Khong, Lynette Moore, Jan E. Liebelt, Andreas W. Schreiber, Sarah L. King-Smith, Tristan S.E. Hardy, Matilda R. Jackson, Christopher P. Barnett, Hamish S. Scott

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)
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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.

Original languageEnglish
Pages (from-to)180-189
Number of pages10
JournalNature Medicine
Issue number1
Publication statusPublished - Jan 2023
Externally publishedYes


  • Disease genetics
  • Genetic testing
  • Medical genomics


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