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

Creative Commons License

Byrne A. B., Arts P., Ha T. T., Kassahn K. S., Pais L. S., O'Donnell-Luria A., ...More

NATURE MEDICINE, vol.29, pp.180-189, 2023 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 29
  • Publication Date: 2023
  • Doi Number: 10.1038/s41591-022-02142-1
  • Journal Name: NATURE MEDICINE
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Public Affairs Index, Veterinary Science Database, DIALNET
  • Page Numbers: pp.180-189
  • Ankara University Affiliated: Yes

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.