학술논문

Genomic autopsy to identify underlying causes of pregnancy loss and perinatal death.
Document Type
Academic Journal
Author
Byrne AB; Department of Genetics and Molecular Pathology, Centre for Cancer Biology, an alliance between SA Pathology and the University of South Australia, Adelaide, South Australia, Australia.; UniSA Clinical and Health Sciences, University of South Australia, Adelaide, South Australia, Australia.; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Arts P; Department of Genetics and Molecular Pathology, Centre for Cancer Biology, an alliance between SA Pathology and the University of South Australia, Adelaide, South Australia, Australia.; Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.; Ha TT; Department of Genetics and Molecular Pathology, Centre for Cancer Biology, an alliance between SA Pathology and the University of South Australia, Adelaide, South Australia, Australia.; ACRF Genomics Facility, Centre for Cancer Biology, an alliance between SA Pathology and the University of South Australia, Adelaide, South Australia, Australia.; Kassahn KS; Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.; Department of Genetics and Molecular Pathology, SA Pathology, Adelaide, South Australia, Australia.; Pais LS; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; O'Donnell-Luria A; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Division of Genetics and Genomics, Boston Childrens Hospital, Boston, MA, USA.; Babic M; Department of Genetics and Molecular Pathology, Centre for Cancer Biology, an alliance between SA Pathology and the University of South Australia, Adelaide, South Australia, Australia.; Frank MSB; Department of Genetics and Molecular Pathology, Centre for Cancer Biology, an alliance between SA Pathology and the University of South Australia, Adelaide, South Australia, Australia.; Feng J; UniSA Clinical and Health Sciences, University of South Australia, Adelaide, South Australia, Australia.; ACRF Genomics Facility, Centre for Cancer Biology, an alliance between SA Pathology and the University of South Australia, Adelaide, South Australia, Australia.; Wang P; ACRF Genomics Facility, Centre for Cancer Biology, an alliance between SA Pathology and the University of South Australia, Adelaide, South Australia, Australia.; Lawrence DM; ACRF Genomics Facility, Centre for Cancer Biology, an alliance between SA Pathology and the University of South Australia, Adelaide, South Australia, Australia.; Department of Genetics and Molecular Pathology, SA Pathology, Adelaide, South Australia, Australia.; Eshraghi L; Department of Genetics and Molecular Pathology, Centre for Cancer Biology, an alliance between SA Pathology and the University of South Australia, Adelaide, South Australia, Australia.; Arriola L; Department of Genetics and Molecular Pathology, Centre for Cancer Biology, an alliance between SA Pathology and the University of South Australia, Adelaide, South Australia, Australia.; ACRF Genomics Facility, Centre for Cancer Biology, an alliance between SA Pathology and the University of South Australia, Adelaide, South Australia, Australia.; Toubia J; ACRF Genomics Facility, Centre for Cancer Biology, an alliance between SA Pathology and the University of South Australia, Adelaide, South Australia, Australia.; Nguyen H; Department of Genetics and Molecular Pathology, SA Pathology, Adelaide, South Australia, Australia.; McGillivray G; Victorian Clinical Genetics Services, Murdoch Children's Research Institute and Royal Women's Hospital, Melbourne, Victoria, Australia.; Pinner J; Centre for Clinical Genetics, Sydney Children's Hospitals Network - Randwick, Sydney, New South Wales, Australia.; School of Women's and Children's Health, University of NSW, Sydney, New South Wales, Australia.; McKenzie F; Genetic Services of Western Australia, Perth, Western Australia, Australia.; School of Paediatrics and Child Health, University of Western Australia, Perth, Western Australia, Australia.; Morrow R; Department of Genetics and Molecular Pathology, Centre for Cancer Biology, an alliance between SA Pathology and the University of South Australia, Adelaide, South Australia, Australia.; Department of Anatomical Pathology, SA Pathology, Women's and Children's Hospital, North Adelaide, South Australia, Australia.; Lipsett J; Department of Anatomical Pathology, SA Pathology, Women's and Children's Hospital, North Adelaide, South Australia, Australia.; Manton N; Department of Anatomical Pathology, SA Pathology, Women's and Children's Hospital, North Adelaide, South Australia, Australia.; Khong TY; Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.; Department of Anatomical Pathology, SA Pathology, Women's and Children's Hospital, North Adelaide, South Australia, Australia.; Moore L; Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.; Department of Anatomical Pathology, SA Pathology, Women's and Children's Hospital, North Adelaide, South Australia, Australia.; Liebelt JE; Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.; Paediatric and Reproductive Genetics Unit, South Australian Clinical Genetics Service, Women's and Children's Hospital, North Adelaide, South Australia, Australia.; Repromed, Dulwich, South Australia, Australia.; Schreiber AW; UniSA Clinical and Health Sciences, University of South Australia, Adelaide, South Australia, Australia.; ACRF Genomics Facility, Centre for Cancer Biology, an alliance between SA Pathology and the University of South Australia, Adelaide, South Australia, Australia.; School of Biological Sciences, University of Adelaide, Adelaide, South Australia, Australia.; King-Smith SL; Department of Genetics and Molecular Pathology, Centre for Cancer Biology, an alliance between SA Pathology and the University of South Australia, Adelaide, South Australia, Australia.; Australian Genomics, Parkville, Victoria, Australia.; Hardy TSE; Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.; Department of Genetics and Molecular Pathology, SA Pathology, Adelaide, South Australia, Australia.; Repromed, Dulwich, South Australia, Australia.; Jackson MR; Department of Genetics and Molecular Pathology, Centre for Cancer Biology, an alliance between SA Pathology and the University of South Australia, Adelaide, South Australia, Australia.; Australian Genomics, Parkville, Victoria, Australia.; Barnett CP; Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia. christopher.barnett@sa.gov.au.; Paediatric and Reproductive Genetics Unit, South Australian Clinical Genetics Service, Women's and Children's Hospital, North Adelaide, South Australia, Australia. christopher.barnett@sa.gov.au.; Scott HS; Department of Genetics and Molecular Pathology, Centre for Cancer Biology, an alliance between SA Pathology and the University of South Australia, Adelaide, South Australia, Australia. hamish.scott@sa.gov.au.; UniSA Clinical and Health Sciences, University of South Australia, Adelaide, South Australia, Australia. hamish.scott@sa.gov.au.; Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia. hamish.scott@sa.gov.au.; ACRF Genomics Facility, Centre for Cancer Biology, an alliance between SA Pathology and the University of South Australia, Adelaide, South Australia, Australia. hamish.scott@sa.gov.au.; Department of Genetics and Molecular Pathology, SA Pathology, Adelaide, South Australia, Australia. hamish.scott@sa.gov.au.; Australian Genomics, Parkville, Victoria, Australia. hamish.scott@sa.gov.au.
Source
Publisher: Nature Publishing Company Country of Publication: United States NLM ID: 9502015 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1546-170X (Electronic) Linking ISSN: 10788956 NLM ISO Abbreviation: Nat Med Subsets: MEDLINE
Subject
Language
English
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.
(© 2023. Crown.)