npj Genomic Medicine (May 2023)
Diagnostic yield of pediatric and prenatal exome sequencing in a diverse population
- Anne Slavotinek,
- Shannon Rego,
- Nuriye Sahin-Hodoglugil,
- Mark Kvale,
- Billie Lianoglou,
- Tiffany Yip,
- Hannah Hoban,
- Simon Outram,
- Beatrice Anguiano,
- Flavia Chen,
- Jeremy Michelson,
- Roberta M. Cilio,
- Cynthia Curry,
- Renata C. Gallagher,
- Marisa Gardner,
- Rachel Kuperman,
- Bryce Mendelsohn,
- Elliott Sherr,
- Joseph Shieh,
- Jonathan Strober,
- Allison Tam,
- Jessica Tenney,
- William Weiss,
- Amy Whittle,
- Garrett Chin,
- Amanda Faubel,
- Hannah Prasad,
- Yusuph Mavura,
- Jessica Van Ziffle,
- W. Patrick Devine,
- Ugur Hodoglugil,
- Pierre-Marie Martin,
- Teresa N. Sparks,
- Barbara Koenig,
- Sara Ackerman,
- Neil Risch,
- Pui-Yan Kwok,
- Mary E. Norton
Affiliations
- Anne Slavotinek
- Department of Pediatrics, University of California, San Francisco
- Shannon Rego
- Department of Pediatrics, University of California, San Francisco
- Nuriye Sahin-Hodoglugil
- Institute for Human Genetics, University of California San Francisco
- Mark Kvale
- Institute for Human Genetics, University of California San Francisco
- Billie Lianoglou
- Department of Surgery, University of California, San Francisco
- Tiffany Yip
- Department of Pediatrics, University of California, San Francisco
- Hannah Hoban
- Department of Pediatrics, University of California, San Francisco
- Simon Outram
- Institute for Health & Aging, School of Nursing, University of California San Francisco
- Beatrice Anguiano
- Institute for Human Genetics, University of California San Francisco
- Flavia Chen
- Institute for Human Genetics, University of California San Francisco
- Jeremy Michelson
- Institute of Human Nutrition, Columbia University Medical Center
- Roberta M. Cilio
- Division of Pediatric Neurology, Department of Pediatrics, University of Louvain
- Cynthia Curry
- Genetic Medicine, University of California, San Francisco
- Renata C. Gallagher
- Department of Pediatrics, University of California, San Francisco
- Marisa Gardner
- Department of Neurology, UCSF Benioff Children’s Hospital Oakland
- Rachel Kuperman
- Department of Neurology, UCSF Benioff Children’s Hospital Oakland
- Bryce Mendelsohn
- Division of Genetics, Kaiser Permanente Oakland Medical Center
- Elliott Sherr
- Division of Child Neurology, Department of Neurology, University of California, San Francisco
- Joseph Shieh
- Department of Pediatrics, University of California, San Francisco
- Jonathan Strober
- Division of Child Neurology, Department of Neurology, University of California, San Francisco
- Allison Tam
- Department of Pediatrics, University of California, San Francisco
- Jessica Tenney
- Department of Pediatrics, University of California, San Francisco
- William Weiss
- Division of Child Neurology, Zuckerberg San Francisco General Hospital, San Francisco
- Amy Whittle
- Division of Pediatrics, Zuckerberg San Francisco General Hospital, San Francisco
- Garrett Chin
- Institute for Human Genetics, University of California San Francisco
- Amanda Faubel
- Department of Surgery, University of California, San Francisco
- Hannah Prasad
- Institute for Human Genetics, University of California San Francisco
- Yusuph Mavura
- Institute for Human Genetics, University of California San Francisco
- Jessica Van Ziffle
- Department of Pathology, University of California San Francisco
- W. Patrick Devine
- Department of Pathology, University of California San Francisco
- Ugur Hodoglugil
- Genomic Medicine Laboratory, University of California San Francisco
- Pierre-Marie Martin
- Institute for Human Genetics, University of California San Francisco
- Teresa N. Sparks
- Institute for Human Genetics, University of California San Francisco
- Barbara Koenig
- Institute for Human Genetics, University of California San Francisco
- Sara Ackerman
- Institute for Health & Aging, School of Nursing, University of California San Francisco
- Neil Risch
- Institute for Human Genetics, University of California San Francisco
- Pui-Yan Kwok
- Cardiovascular Research Institute, University of California San Francisco
- Mary E. Norton
- Institute for Human Genetics, University of California San Francisco
- DOI
- https://doi.org/10.1038/s41525-023-00353-0
- Journal volume & issue
-
Vol. 8,
no. 1
pp. 1 – 10
Abstract
Abstract The diagnostic yield of exome sequencing (ES) has primarily been evaluated in individuals of European ancestry, with less focus on underrepresented minority (URM) and underserved (US) patients. We evaluated the diagnostic yield of ES in a cohort of predominantly US and URM pediatric and prenatal patients suspected to have a genetic disorder. Eligible pediatric patients had multiple congenital anomalies and/or neurocognitive disabilities and prenatal patients had one or more structural anomalies, disorders of fetal growth, or fetal effusions. URM and US patients were prioritized for enrollment and underwent ES at a single academic center. We identified definitive positive or probable positive results in 201/845 (23.8%) patients, with a significantly higher diagnostic rate in pediatric (26.7%) compared to prenatal patients (19.0%) (P = 0.01). For both pediatric and prenatal patients, the diagnostic yield and frequency of inconclusive findings did not differ significantly between URM and non-URM patients or between patients with US status and those without US status. Our results demonstrate a similar diagnostic yield of ES between prenatal and pediatric URM/US patients and non-URM/US patients for positive and inconclusive results. These data support the use of ES to identify clinically relevant variants in patients from diverse populations.
