Genome sequencing as a first-line diagnostic test for hospitalized infants

Kevin M. Bowling, Michelle L. Thompson, Candice R. Finnila, Susan M. Hiatt, Donald R. Latner, Michelle D. Amaral, James M.J. Lawlor, Kelly M. East, Meagan E. Cochran, Veronica Greve, Whitley V. Kelley, David E. Gray, Stephanie A. Felker, Hannah Meddaugh, Ashley Cannon, Amanda Luedecke, Kelly E. Jackson, Laura G. Hendon, Hillary M. Janani, Marla JohnstonLee Ann Merin, Sarah L. Deans, Carly Tuura, Heather Williams, Kelly Laborde, Matthew B. Neu, Jessica Patrick-Esteve, Anna C.E. Hurst, Jegen Kandasamy, Wally Carlo, Kyle B. Brothers, Brian M. Kirmse, Renate Savich, Duane Superneau, Steven B. Spedale, Sara J. Knight, Gregory S. Barsh, Bruce R. Korf, Gregory M. Cooper

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Purpose: SouthSeq is a translational research study that undertook genome sequencing (GS) for infants with symptoms suggestive of a genetic disorder. Recruitment targeted racial/ethnic minorities and rural, medically underserved areas in the Southeastern United States, which are historically underrepresented in genomic medicine research. Methods: GS and analysis were performed for 367 infants to detect disease-causal variation concurrent with standard of care evaluation and testing. Results: Definitive diagnostic (DD) or likely diagnostic (LD) genetic findings were identified in 30% of infants, and 14% of infants harbored an uncertain result. Only 43% of DD/LD findings were identified via concurrent clinical genetic testing, suggesting that GS testing is better for obtaining early genetic diagnosis. We also identified phenotypes that correlate with the likelihood of receiving a DD/LD finding, such as craniofacial, ophthalmologic, auditory, skin, and hair abnormalities. We did not observe any differences in diagnostic rates between racial/ethnic groups. Conclusion: We describe one of the largest-to-date GS cohorts of ill infants, enriched for African American and rural patients. Our results show the utility of GS because it provides early-in-life detection of clinically relevant genetic variations not detected by current clinical genetic testing, particularly for infants exhibiting certain phenotypic features.

Original languageEnglish
Pages (from-to)851-861
Number of pages11
JournalGenetics in Medicine
Issue number4
StatePublished - Apr 2022


  • Diagnostic yield
  • Genetic diagnosis
  • Genome sequencing
  • Infants
  • Utility


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