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


Journal

Nature medicine
ISSN: 1546-170X
Titre abrégé: Nat Med
Pays: United States
ID NLM: 9502015

Informations de publication

Date de publication:
01 2023
Historique:
received: 29 12 2021
accepted: 22 11 2022
pubmed: 20 1 2023
medline: 27 1 2023
entrez: 19 1 2023
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 36658419
doi: 10.1038/s41591-022-02142-1
pii: 10.1038/s41591-022-02142-1
pmc: PMC10333122
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

180-189

Subventions

Organisme : NHGRI NIH HHS
ID : UM1 HG008900
Pays : United States

Investigateurs

François Aguet (F)
Harindra M Arachchi (HM)
Christina A Austin-Tse (CA)
Larry Babb (L)
Samantha M Baxter (SM)
Harrison Brand (H)
Jaime Chang (J)
Katherine R Chao (KR)
Ryan L Collins (RL)
Beryl Cummings (B)
Kayla Delano (K)
Stephanie P DiTroia (SP)
Eleina England (E)
Emily Evangelista (E)
Selin Everett (S)
Laurent C Francioli (LC)
Jack Fu (J)
Vijay S Ganesh (VS)
Kiran V Garimella (KV)
Laura D Gauthier (LD)
Julia K Goodrich (JK)
Sanna Gudmundsson (S)
Stacey J Hall (SJ)
Yongqing Huang (Y)
Steve Jahl (S)
Kristen M Laricchia (KM)
Kathryn E Larkin (KE)
Monkol Lek (M)
Gabrielle Lemire (G)
Rachel B Lipson (RB)
Alysia Kern Lovgren (AK)
Daniel G MacArthur (DG)
Brian E Mangilog (BE)
Stacy Mano (S)
Jamie L Marshall (JL)
Thomas E Mullen (TE)
Kevin K Nguyen (KK)
Emily O'Heir (E)
Melanie C O'Leary (MC)
Ikeoluwa A Osei-Owusu (IA)
Jorge Perez de Acha Chavez (JP)
Emma Pierce-Hoffman (E)
Heidi L Rehm (HL)
Jillian Serrano (J)
Moriel Singer-Berk (M)
Hana Snow (H)
Matthew Solomonson (M)
Rachel G Son (RG)
Abigail Sveden (A)
Michael Talkowski (M)
Grace Tiao (G)
Miriam S Udler (MS)
Zaheer Valivullah (Z)
Elise Valkanas (E)
Grace E VanNoy (GE)
Qingbo S Wang (QS)
Nicholas A Watts (NA)
Ben Weisburd (B)
Clara E Williamson (CE)
Michael W Wilson (MW)
Lauren Witzgall (L)
Monica H Wojcik (MH)
Isaac Wong (I)
Jordan C Wood (JC)
Shifa Zhang (S)
Disna Abeysuriya (D)
Lesley C Ades (LC)
David J Amor (DJ)
Susan Arbuckle (S)
Madhura Bakshi (M)
Bligh Berry (B)
Tiffany Boughtwood (T)
Adam Bournazos (A)
Alessandra Bray (A)
Fiona Chan (F)
Yuen Chan (Y)
Clara Chung (C)
Jonathan Clark (J)
Jackie Collett (J)
Alison Colley (A)
Felicity Collins (F)
Sandra Cooper (S)
Mark A Corbett (MA)
Jane E Dahlstrom (JE)
Peter Dargaville (P)
Janene Davies (J)
Tenielle Davis (T)
Jarrad Dearman (J)
Jayanthi Dissanayake (J)
Julia Dobbins (J)
Helen Doyle (H)
Andrew Dubowsky (A)
Matt Edwards (M)
Lisa J Ewans (LJ)
Mitali Fadia (M)
Andrew Fennell (A)
Keri Finlay (K)
Andrew French (A)
Kathryn Friend (K)
Alison E Gardner (AE)
Jozef Gecz (J)
Nicole Graf (N)
Eric A Haan (EA)
Georgina Hollingsworth (G)
Ari E Horton (AE)
Denise Howting (D)
Matthew F Hunter (MF)
Gareth Jevon (G)
Benjamin Kamien (B)
Debra Kennedy (D)
T Yee Khong (TY)
Michael Krivanek (M)
Thessa Kroes (T)
Emma I Krzesinski (EI)
Edward Kwan (E)
Stephanie Lau (S)
Shannon LeBlanc (S)
Jan Liebelt (J)
Suzanna Lindsey-Temple (S)
Jill Lipsett (J)
Christine K C Loo (CKC)
Julia Low (J)
Amali Mallawaarachchi (A)
Nick Manton (N)
Admire Matsika (A)
Tessa Mattiske (T)
Julie McGaughran (J)
Lesley McGregor (L)
Namita Mittal (N)
Ali Moghimi (A)
Lynette Moore (L)
Hatice Mutlu Albayrak (HM)
Jessica Ng (J)
Jillian Nicholl (J)
Nicholas Pachter (N)
John Papadimitriou (J)
Renae Parker (R)
Sarah Parsons (S)
Chirag Patel (C)
Rhonda Pawlowski (R)
Luis A Perez-Jurado (LA)
Jason R Pinner (JR)
Katerina Politis (K)
Cathryn Poulton (C)
Theresa Power (T)
Michael Quinn (M)
Sulekha Rajagopalan (S)
Matthew Regan (M)
Jonathan Rodgers (J)
Steuart Rorke (S)
Rani Sachdev (R)
Suzanne Sallevelt (S)
Sarah A Sandaradura (SA)
Maryam Shamassi (M)
Roshan Shamon (R)
Isabella Sherburn (I)
Jennie Slee (J)
Annalisa Solinas (A)
Ella Sugo (E)
Elizabeth Thompson (E)
Sagarika Tripathy (S)
Anand Vasudevan (A)
Melisa Vazquez (M)
Kunal Verma (K)
Mthulisi Viki (M)
Mathew Wallis (M)
Dani L Webber (DL)
Martin Weber (M)
Karen Whale (K)
Meredith Wilson (M)
Lisa Worgan (L)
Sui Yu (S)

Commentaires et corrections

Type : CommentIn
Type : ErratumIn

Informations de copyright

© 2023. Crown.

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Auteurs

Alicia B 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.

Peer 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.

Thuong T 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.

Karin S Kassahn (KS)

Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.
Department of Genetics and Molecular Pathology, SA Pathology, Adelaide, South Australia, Australia.

Lynn S Pais (LS)

Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Anne O'Donnell-Luria (A)

Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Division of Genetics and Genomics, Boston Childrens Hospital, Boston, MA, USA.

Milena 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.

Mahalia S B 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.

Jinghua 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.

Paul Wang (P)

ACRF Genomics Facility, Centre for Cancer Biology, an alliance between SA Pathology and the University of South Australia, Adelaide, South Australia, Australia.

David M 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.

Leila 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.

Luis 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.

John Toubia (J)

ACRF Genomics Facility, Centre for Cancer Biology, an alliance between SA Pathology and the University of South Australia, Adelaide, South Australia, Australia.

Hung Nguyen (H)

Department of Genetics and Molecular Pathology, SA Pathology, Adelaide, South Australia, Australia.

George McGillivray (G)

Victorian Clinical Genetics Services, Murdoch Children's Research Institute and Royal Women's Hospital, Melbourne, Victoria, Australia.

Jason 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.

Fiona 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.

Rebecca 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.

Jill Lipsett (J)

Department of Anatomical Pathology, SA Pathology, Women's and Children's Hospital, North Adelaide, South Australia, Australia.

Nick Manton (N)

Department of Anatomical Pathology, SA Pathology, Women's and Children's Hospital, North Adelaide, South Australia, Australia.

T Yee 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.

Lynette 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.

Jan E 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.

Andreas W 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.

Sarah L 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.

Tristan S E 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.

Matilda R 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.

Christopher P 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.

Hamish S 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.

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