Journal article

A prospective evaluation of whole-exome sequencing as a first-tier molecular test in infants with suspected monogenic disorders

Zornitza Stark, Tiong Y Tan, Belinda Chong, Gemma R Brett, Patrick Yap, Maie Walsh, Alison Yeung, Heidi Peters, Dylan Mordaunt, Shannon Cowie, David J Amor, Ravi Savarirayan, George McGillivray, Lilian Downie, Paul G Ekert, Christiane Theda, Paul A James, Joy Yaplito-Lee, Monique M Ryan, Richard J Leventer Show all



PURPOSE: To prospectively evaluate the diagnostic and clinical utility of singleton whole-exome sequencing (WES) as a first-tier test in infants with suspected monogenic disease. METHODS: Singleton WES was performed as a first-tier sequencing test in infants recruited from a single pediatric tertiary center. This occurred in parallel with standard investigations, including single- or multigene panel sequencing when clinically indicated. The diagnosis rate, clinical utility, and impact on management of singleton WES were evaluated. RESULTS: Of 80 enrolled infants, 46 received a molecular genetic diagnosis through singleton WES (57.5%) compared with 11 (13.75%) who underwent standard investiga..

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Funding Acknowledgements

This study was funded by the members of the Melbourne Genomics Health Alliance and the State Government of Victoria (Department of Health and Human Services). We thank the patients and families for participating in this study. We are grateful to Rodney Hunt, Amanda Moody, David Tingay, John Mills, Michael Stewart, Anastasia Pellicano, Leah Hickey, Julia Gunn, Margaret Moran, Mark Mackay, Avihu Boneh, and Cathy Quinlan for referring patients to the study; Kate Pope for genetic counseling support; Nessie Mupfeki for data-management support; and Harriet Dashnow, Gayle Phillip, Anthony Marty, and Andrew Lonie for bioinformatics and database-development support. We also acknowledge the Melbourne Genomics Health Alliance Steering Group, the Clinical Genomics and Bioinformatics Advisory Group, and the Clinical Genomics Advisory Group for establishing the systems and standards applied in this study.