Nationwide, Couple-Based Genetic Carrier Screening

Edwin P Kirk¹, Martin B Delatycki¹, Alison D Archibald¹, Erin Tutty¹, Jade Caruana¹, Jane L Halliday¹, Sharon Lewis¹, Belinda J McClaren¹, Ainsley J Newson¹, Lisa Dive¹, Stephanie Best¹, Janet C Long¹, Jeffrey Braithwaite¹, Martin J Downes¹, Paul A Scuffham¹, John Massie¹, Kristine Barlow-Stewart¹, Abhi Kulkarni¹, Amy Ruscigno¹, Anaita Kanga-Parabia¹, Bianca Rodrigues¹, Bruce H Bennetts¹, Camron Ebzery¹, Clare Hunt¹, Corrina C Cliffe¹, Crystle Lee¹, Dimitar Azmanov¹, Emily A King¹, Evanthia O Madelli¹, Futao Zhang¹, Gladys Ho¹, Isabelle Danos¹, Jan Liebelt¹, Janice Fletcher¹, Jillian Kennedy¹, John Beilby¹, Jon D Emery¹, Julie McGaughran¹, Justine E Marum¹, Katrina Scarff¹, Katrina Fisk¹, Katrina Harrison¹, Kirsten Boggs¹, Lana Giameos¹, Lara Fitzgerald¹, Lauren Thomas¹, Leslie Burnett¹, Lucinda Freeman¹, Madeleine Harris¹, Marina Berbic¹, Mark R Davis¹, Marta Cifuentes Ochoa¹, Mathew Wallis¹, Meaghan Wall¹, Melissa T M Chow¹, Monica M Ferrie¹, Nicholas Pachter¹, Nila Quayum¹, Nitzan Lang¹, Praveena Kasi Pandy¹, Rachael Casella¹, Richard J N Allcock¹, Royston Ong¹, Samantha Edwards¹, Samantha Sundercombe¹, Sarah Jelenich¹, Sarah Righetti¹, Sebastian Lunke¹, Sharanbeer Kaur¹, Sharyn Stock-Myer¹, Stefanie Eggers¹, Susan P Walker¹, Tahlia Theodorou¹, Tara Catchpool¹, Tenielle Clinch¹, Tony Roscioli¹, Tristan Hardy¹, Ying Zhu¹, Zoe Fehlberg¹, Tiffany F Boughtwood¹, Nigel G Laing¹; Mackenzie’s Mission Investigators; Mackenzie's Mission Investigators

Collaborators, Affiliations

Collaborators

Edwin P Kirk, Martin B Delatycki, Alison D Archibald, Erin Tutty, Jade Caruana, Jane L Halliday, Sharon Lewis, Belinda J McClaren, Ainsley J Newson, Lisa Dive, Stephanie Best, Janet C Long, Jeffrey Braithwaite, Martin J Downes, Paul A Scuffham, John Massie, Kristine Barlow-Stewart, Abhi Kulkarni, Amy Ruscigno, Anaita Kanga-Parabia, Bianca Rodrigues, Bruce H Bennetts, Camron Ebzery, Clare Hunt, Corrina C Cliffe, Crystle Lee, Dimitar Azmanov, Emily A King, Evanthia O Madelli, Futao Zhang, Gladys Ho, Isabelle Danos, Jan Liebelt, Janice Fletcher, Jillian Kennedy, John Beilby, Jon D Emery, Julie McGaughran, Justine E Marum, Kate Scarff, Katrina Fisk, Katrina Harrison, Kirsten Boggs, Lana Giameos, Lara Fitzgerald, Lauren Thomas, Leslie Burnett, Lucinda Freeman, Madeleine Harris, Marina Berbic, Mark R Davis, Marta Cifuentes Ochoa, Mathew Wallis, Meg Wall, Melissa Chow, Monica M Ferrie, Nicholas Pachter, Nila Quayum, Nitzan Lang, Praveena Kasi Pandy, Rachael Casella, Richard J N Allcock, Royston Ong, Samantha Edwards, Samantha Sundercombe, Sarah Jelenich, Sarah Righetti, Sebastian Lunke, Sharanbeer Kaur, Sharyn Stockmyer, Stefanie Eggers, Susan P Walker, Tahlia Theodorou, Tara Catchpool, Tenielle Clinch, Tony Roscioli, Tristan Hardy, Ying Zhu, Zoe Fehlberg, Tiffany F Boughtwood, Nigel G Laing, Alan Ma, Alisha Monaco, Alison Colley, Anja Ravine, Anna Richards, Ben Kamien, Bethany Wadling, Cheryl Wise, Chiyan Lau, Clara Chung, Clara Gaff, Cliff Meldrum, Conor Rowntree, Damien Bruno, David Amor, Diana Ky, Emily Oates, Eric Lee, George Elakis, Georgina Hollingsworth, Glenda Mullan, Grace Androga, Guus Teunisse, Hang Yin, Huynh Truong, Jason Lum, Jason Tseung, Jesse Pinguinha, Jessica Lu, Karen Carpenter, Kate Dunlop, Katie Ashton, Kay Khan, Kim Thien An, Kym Mina, Lauren Burnell, Lucy Gilkes, Lyle Gurrin, Madhura Bakshi, Mark Pertile, Melanie Galea, Melissa Cullen, Michael Buckley, Michael Fietz, Michelle Farrar, Nasrin Javid, Natalia Smietanka, Nathan Petricevic, Patricia Sullivan, Paul Gray, Peter Kuab, Rebecca Walsh, Robyn Jamieson, Sandra Cooper, Sarah Lang, Shuxiang Goh, Simon Morgan, Stephen Robson, Steve Robertson, Sulekha Rajagopalan, Tianjiao Wang, Xiaofeng Xie

Affiliation

¹ From the Centre for Clinical Genetics, Sydney Children's Hospital (E.P.K., K.B., S.R., S.K.), NSW Health Pathology Randwick Genomics Laboratory (E.P.K., B.R., C.C.C., F.Z., J.F., M.B., N.Q., S.R., S.K., T.R., Y.Z.), the School of Clinical Medicine (E.P.K., M.B.), the School of Women's and Children's Health (L. Freeman, S.R., S.K.), and the Randwick Clinical Campus, Neuroscience Research Australia (Y.Z.), University of New South Wales, Randwick, Victorian Clinical Genetics Services (M.B.D., A.D.A., A.K.-P., C.H., C.L., I.D., J.E.M., K.S., L.G., L.T., M.C.O., M. Wall, M.T.M.C., M.M.F., N.L., S. Lunke, S. Eggers), the Bruce Lefroy Centre, Murdoch Children's Research Institute (M.B.D., E.A.K.), the Department of Paediatrics (M.B.D., A.D.A., E.T., J.L.H., S. Lewis, B.J.M., J. Massie, E.A.K., Z.F.), the Department of General Practice and Centre for Cancer Research (J.D.E.), and the Department of Pathology (Sebastian Lunke), University of Melbourne, Murdoch Children's Research Institute (A.D.A., E.T., J.C., J.L.H., S. Lewis, B.J.M., J. Massie, A.R., E.A.K., E.O.M., L.G., M.H., S.J., S. Lunke, S. Eggers, T.F.B.), and Australian Genomics (J.C., A.J.N., S.B., Jeffrey Braithwaite, E.O.M., K.B., S.J., Z.F., T.F.B.), Parkville, VIC, the Faculty of Medicine and Health, Sydney School of Public Health, Sydney Health Ethics, University of Sydney, Camperdown, NSW (A.J.N., L.D.), the Graduate School of Health, University of Technology Sydney (L.D., L. Freeman), Macquarie University, Australian Institute of Health Innovation (J.C.L., J. Braithwaite, T.T.), and the Faculty of Medicine and Health, University of New South Wales (K.B.-S.), Sydney (R.C.), the Peter MacCallum Cancer Centre (S.B.), the Victorian Comprehensive Cancer Centre (S.B.), the Sir Peter MacCallum Department of Oncology (S.B.) and the Department of Obstetrics and Gynaecology (S.P.W.), University of Melbourne, the Department of Respiratory Medicine and Children's Bioethics Centre, the Royal Children's Hospital (J. Massie), Genomic Diagnostics (A.K.), and Virtus Health, Virtus Genetics (S.S.-M.), Melbourne, VIC, Menzies Health Institute Queensland, Griffith University, and Griffith University School of Medicine and Dentistry, Gold Coast (M.J.D., P.A.S.), the Northern Clinical School, Faculty of Medicine and Health (K.B.S., L.B.), and Royal North Shore Hospital, Kolling Institute, Cancer Genetics Laboratory (Y.Z.), University of Sydney, St. Leonards, NSW, SA Pathology (A.K., T.H.), South Australian Clinical Genetics Service (J.L.) and the Pediatric and Reproductive Genetics Unit (L. Fitzgerald), Women's and Children's Hospital, and Repromed (J.L.), Adelaide, the Children's Hospital at Westmead, Sydney Genome Diagnostics (B.H.B., G.H., K.F.), the Specialty of Genomic Medicine, Faculty of Medicine and Health, the Children's Hospital at Westmead Clinical School, University of Sydney (B.H.B., G.H., K.F.), and the Department of Clinical Genetics, the Children's Hospital at Westmead (K.B.), Westmead, NSW, Genetic Health Queensland, Royal Brisbane and Women's Hospital (C.E., J. McGaughran, T. Clinch), and the School of Medicine, University of Queensland (Julie McGaughran), Brisbane, the Department of Diagnostic Genomics, PathWest Laboratory Medicine (D.A., M.R.D., P.K.P., R.J.N.A., R.O., T. Catchpool, N.G.L.), the School of Biological Sciences, Centre for Genetic Origins of Health and Disease (J. Beilby), the Centre for Medical Research (M.R.D., R.O., N.G.L.), and the Faculty of Health and Medical Sciences (N.P.), University of Western Australia, and Harry Perkins Institute of Medical Research (R.O., Samantha Edwards, N.G.L.), Nedlands, the Department of Pathology and Laboratory Medicine, Medical School, University of Western Australia (D.A.), and Genetic Services of Western Australia, King Edward Memorial Hospital (J.K., N.P.), Perth, the Tasmanian Clinical Genetics Service (K.H., M. Wallis) and the School of Medicine and Menzies Institute for Medical Research (M. Wallis), University of Tasmania, Hobart, the Garvan Institute of Medical Research and the School of Clinical Medicine, St. Vincent's Clinical Campus, University of New South Wales, Darlinghurst (L.B.), King Edward Memorial Hospital, Subiaco, WA (N.P.), the School of Biomedical Sciences, University of Western Australia, Crawley (R.J.N.A.), Sonic Healthcare, Douglass Hanly Moir Pathology, Macquarie Park, NSW (S.S.), Mercy Hospital for Women, Mercy Perinatal, Heidelberg, VIC (S.P.W.), and Monash IVF Group, Richmond, VIC (T.H.) - all in Australia; and the International Society for Quality in Health Care, Dublin (J. Braithwaite).

PMID: 39565987
DOI: 10.1056/NEJMoa2314768

Clinical Trial

Nationwide, Couple-Based Genetic Carrier Screening

Edwin P Kirk et al. N Engl J Med. 2024.

. 2024 Nov 21;391(20):1877-1889.

doi: 10.1056/NEJMoa2314768.

Authors

Collaborators

Edwin P Kirk, Martin B Delatycki, Alison D Archibald, Erin Tutty, Jade Caruana, Jane L Halliday, Sharon Lewis, Belinda J McClaren, Ainsley J Newson, Lisa Dive, Stephanie Best, Janet C Long, Jeffrey Braithwaite, Martin J Downes, Paul A Scuffham, John Massie, Kristine Barlow-Stewart, Abhi Kulkarni, Amy Ruscigno, Anaita Kanga-Parabia, Bianca Rodrigues, Bruce H Bennetts, Camron Ebzery, Clare Hunt, Corrina C Cliffe, Crystle Lee, Dimitar Azmanov, Emily A King, Evanthia O Madelli, Futao Zhang, Gladys Ho, Isabelle Danos, Jan Liebelt, Janice Fletcher, Jillian Kennedy, John Beilby, Jon D Emery, Julie McGaughran, Justine E Marum, Kate Scarff, Katrina Fisk, Katrina Harrison, Kirsten Boggs, Lana Giameos, Lara Fitzgerald, Lauren Thomas, Leslie Burnett, Lucinda Freeman, Madeleine Harris, Marina Berbic, Mark R Davis, Marta Cifuentes Ochoa, Mathew Wallis, Meg Wall, Melissa Chow, Monica M Ferrie, Nicholas Pachter, Nila Quayum, Nitzan Lang, Praveena Kasi Pandy, Rachael Casella, Richard J N Allcock, Royston Ong, Samantha Edwards, Samantha Sundercombe, Sarah Jelenich, Sarah Righetti, Sebastian Lunke, Sharanbeer Kaur, Sharyn Stockmyer, Stefanie Eggers, Susan P Walker, Tahlia Theodorou, Tara Catchpool, Tenielle Clinch, Tony Roscioli, Tristan Hardy, Ying Zhu, Zoe Fehlberg, Tiffany F Boughtwood, Nigel G Laing, Alan Ma, Alisha Monaco, Alison Colley, Anja Ravine, Anna Richards, Ben Kamien, Bethany Wadling, Cheryl Wise, Chiyan Lau, Clara Chung, Clara Gaff, Cliff Meldrum, Conor Rowntree, Damien Bruno, David Amor, Diana Ky, Emily Oates, Eric Lee, George Elakis, Georgina Hollingsworth, Glenda Mullan, Grace Androga, Guus Teunisse, Hang Yin, Huynh Truong, Jason Lum, Jason Tseung, Jesse Pinguinha, Jessica Lu, Karen Carpenter, Kate Dunlop, Katie Ashton, Kay Khan, Kim Thien An, Kym Mina, Lauren Burnell, Lucy Gilkes, Lyle Gurrin, Madhura Bakshi, Mark Pertile, Melanie Galea, Melissa Cullen, Michael Buckley, Michael Fietz, Michelle Farrar, Nasrin Javid, Natalia Smietanka, Nathan Petricevic, Patricia Sullivan, Paul Gray, Peter Kuab, Rebecca Walsh, Robyn Jamieson, Sandra Cooper, Sarah Lang, Shuxiang Goh, Simon Morgan, Stephen Robson, Steve Robertson, Sulekha Rajagopalan, Tianjiao Wang, Xiaofeng Xie

Affiliation

¹ From the Centre for Clinical Genetics, Sydney Children's Hospital (E.P.K., K.B., S.R., S.K.), NSW Health Pathology Randwick Genomics Laboratory (E.P.K., B.R., C.C.C., F.Z., J.F., M.B., N.Q., S.R., S.K., T.R., Y.Z.), the School of Clinical Medicine (E.P.K., M.B.), the School of Women's and Children's Health (L. Freeman, S.R., S.K.), and the Randwick Clinical Campus, Neuroscience Research Australia (Y.Z.), University of New South Wales, Randwick, Victorian Clinical Genetics Services (M.B.D., A.D.A., A.K.-P., C.H., C.L., I.D., J.E.M., K.S., L.G., L.T., M.C.O., M. Wall, M.T.M.C., M.M.F., N.L., S. Lunke, S. Eggers), the Bruce Lefroy Centre, Murdoch Children's Research Institute (M.B.D., E.A.K.), the Department of Paediatrics (M.B.D., A.D.A., E.T., J.L.H., S. Lewis, B.J.M., J. Massie, E.A.K., Z.F.), the Department of General Practice and Centre for Cancer Research (J.D.E.), and the Department of Pathology (Sebastian Lunke), University of Melbourne, Murdoch Children's Research Institute (A.D.A., E.T., J.C., J.L.H., S. Lewis, B.J.M., J. Massie, A.R., E.A.K., E.O.M., L.G., M.H., S.J., S. Lunke, S. Eggers, T.F.B.), and Australian Genomics (J.C., A.J.N., S.B., Jeffrey Braithwaite, E.O.M., K.B., S.J., Z.F., T.F.B.), Parkville, VIC, the Faculty of Medicine and Health, Sydney School of Public Health, Sydney Health Ethics, University of Sydney, Camperdown, NSW (A.J.N., L.D.), the Graduate School of Health, University of Technology Sydney (L.D., L. Freeman), Macquarie University, Australian Institute of Health Innovation (J.C.L., J. Braithwaite, T.T.), and the Faculty of Medicine and Health, University of New South Wales (K.B.-S.), Sydney (R.C.), the Peter MacCallum Cancer Centre (S.B.), the Victorian Comprehensive Cancer Centre (S.B.), the Sir Peter MacCallum Department of Oncology (S.B.) and the Department of Obstetrics and Gynaecology (S.P.W.), University of Melbourne, the Department of Respiratory Medicine and Children's Bioethics Centre, the Royal Children's Hospital (J. Massie), Genomic Diagnostics (A.K.), and Virtus Health, Virtus Genetics (S.S.-M.), Melbourne, VIC, Menzies Health Institute Queensland, Griffith University, and Griffith University School of Medicine and Dentistry, Gold Coast (M.J.D., P.A.S.), the Northern Clinical School, Faculty of Medicine and Health (K.B.S., L.B.), and Royal North Shore Hospital, Kolling Institute, Cancer Genetics Laboratory (Y.Z.), University of Sydney, St. Leonards, NSW, SA Pathology (A.K., T.H.), South Australian Clinical Genetics Service (J.L.) and the Pediatric and Reproductive Genetics Unit (L. Fitzgerald), Women's and Children's Hospital, and Repromed (J.L.), Adelaide, the Children's Hospital at Westmead, Sydney Genome Diagnostics (B.H.B., G.H., K.F.), the Specialty of Genomic Medicine, Faculty of Medicine and Health, the Children's Hospital at Westmead Clinical School, University of Sydney (B.H.B., G.H., K.F.), and the Department of Clinical Genetics, the Children's Hospital at Westmead (K.B.), Westmead, NSW, Genetic Health Queensland, Royal Brisbane and Women's Hospital (C.E., J. McGaughran, T. Clinch), and the School of Medicine, University of Queensland (Julie McGaughran), Brisbane, the Department of Diagnostic Genomics, PathWest Laboratory Medicine (D.A., M.R.D., P.K.P., R.J.N.A., R.O., T. Catchpool, N.G.L.), the School of Biological Sciences, Centre for Genetic Origins of Health and Disease (J. Beilby), the Centre for Medical Research (M.R.D., R.O., N.G.L.), and the Faculty of Health and Medical Sciences (N.P.), University of Western Australia, and Harry Perkins Institute of Medical Research (R.O., Samantha Edwards, N.G.L.), Nedlands, the Department of Pathology and Laboratory Medicine, Medical School, University of Western Australia (D.A.), and Genetic Services of Western Australia, King Edward Memorial Hospital (J.K., N.P.), Perth, the Tasmanian Clinical Genetics Service (K.H., M. Wallis) and the School of Medicine and Menzies Institute for Medical Research (M. Wallis), University of Tasmania, Hobart, the Garvan Institute of Medical Research and the School of Clinical Medicine, St. Vincent's Clinical Campus, University of New South Wales, Darlinghurst (L.B.), King Edward Memorial Hospital, Subiaco, WA (N.P.), the School of Biomedical Sciences, University of Western Australia, Crawley (R.J.N.A.), Sonic Healthcare, Douglass Hanly Moir Pathology, Macquarie Park, NSW (S.S.), Mercy Hospital for Women, Mercy Perinatal, Heidelberg, VIC (S.P.W.), and Monash IVF Group, Richmond, VIC (T.H.) - all in Australia; and the International Society for Quality in Health Care, Dublin (J. Braithwaite).

PMID: 39565987
DOI: 10.1056/NEJMoa2314768

Abstract

Background: Genomic sequencing technology allows for identification of reproductive couples with an increased chance, as compared with that in the general population, of having a child with an autosomal recessive or X-linked genetic condition.

Methods: We investigated the feasibility, acceptability, and outcomes of a nationwide, couple-based genetic carrier screening program in Australia as part of the Mackenzie's Mission project. Health care providers offered screening to persons before pregnancy or early in pregnancy. The results obtained from testing at least 1281 genes were provided to the reproductive couples. We aimed to ascertain the psychosocial effects on participants, the acceptability of screening to all participants, and the reproductive choices of persons identified as having an increased chance of having a child with a condition for which we screened.

Results: Among 10,038 reproductive couples enrolled in the study, 9107 (90.7%) completed screening, and 175 (1.9%) were newly identified as having an increased chance of having a child with a genetic condition for which we screened. These conditions involved pathogenic variants in 90 different genes; 74.3% of the conditions were autosomal recessive. Three months after receiving the results, 76.6% of the couples with a newly identified increased chance had used or planned to use reproductive interventions to avoid having an affected child. Those newly identified as having an increased chance had greater anxiety than those with a low chance. The median level of decisional regret was low in all result groups, and 98.9% of participants perceived screening to be acceptable.

Conclusions: Couple-based reproductive genetic carrier screening was largely acceptable to participants and was used to inform reproductive decision making. The delivery of screening to a diverse and geographically dispersed population was feasible. (Funded by the Medical Research Future Fund of the Australian government; ClinicalTrials.gov number, NCT04157595.).

PubMed Disclaimer

Comment in

Nationwide, Couple-Based Genetic Carrier Screening.
Chotiprasidhi P, Veres LN, Wangensteen KJ. Chotiprasidhi P, et al. N Engl J Med. 2025 Feb 27;392(9):929-930. doi: 10.1056/NEJMc2500317. N Engl J Med. 2025. PMID: 40009813 No abstract available.
Nationwide, Couple-Based Genetic Carrier Screening. Reply.
Delatycki MB, Kirk EP, Laing NG. Delatycki MB, et al. N Engl J Med. 2025 Feb 27;392(9):930. doi: 10.1056/NEJMc2500317. N Engl J Med. 2025. PMID: 40009814 No abstract available.

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Nationwide, Couple-Based Genetic Carrier Screening

Collaborators

Affiliation

Nationwide, Couple-Based Genetic Carrier Screening

Authors

Collaborators

Affiliation

Abstract

Comment in

Publication types

MeSH terms

Associated data

Grants and funding

LinkOut - more resources

Full Text Sources

Medical