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

Genet Med. 2022 Apr;24(4):851-861. doi: 10.1016/j.gim.2021.11.020. Epub 2021 Nov 27.


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.

Keywords: Diagnostic yield; Genetic diagnosis; Genome sequencing; Infants; Utility.

Publication types

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

MeSH terms

  • Base Sequence
  • Chromosome Mapping
  • Diagnostic Tests, Routine*
  • Genetic Testing* / methods
  • Genomics
  • Humans