@article{88c1ae3e002f4c868f7e844318c7da46,
title = "Genome sequencing as a first-line diagnostic test for hospitalized infants",
abstract = "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",
author = "Bowling, {Kevin M.} and Thompson, {Michelle L.} and Finnila, {Candice R.} and Hiatt, {Susan M.} and Latner, {Donald R.} and Amaral, {Michelle D.} and Lawlor, {James M.J.} and East, {Kelly M.} and Cochran, {Meagan E.} and Veronica Greve and Kelley, {Whitley V.} and Gray, {David E.} and Felker, {Stephanie A.} and Hannah Meddaugh and Ashley Cannon and Amanda Luedecke and Jackson, {Kelly E.} and Hendon, {Laura G.} and Janani, {Hillary M.} and Marla Johnston and Merin, {Lee Ann} and Deans, {Sarah L.} and Carly Tuura and Heather Williams and Kelly Laborde and Neu, {Matthew B.} and Jessica Patrick-Esteve and Hurst, {Anna C.E.} and Jegen Kandasamy and Wally Carlo and Brothers, {Kyle B.} and Kirmse, {Brian M.} and Renate Savich and Duane Superneau and Spedale, {Steven B.} and Knight, {Sara J.} and Barsh, {Gregory S.} and Korf, {Bruce R.} and Cooper, {Gregory M.}",
note = "Funding Information: We are grateful to the patients and their families who contributed to this study. We thank the HudsonAlpha Software Development and Informatics team and the Clinical Services Laboratory who contributed to data acquisition and analysis. The SouthSeq project (U01HG007301) was supported by the Clinical Sequencing Evidence-Generating Research consortium, which is funded by the National Human Genome Research Institute with cofunding from the National Institute on Minority Health and Health Disparities and the National Cancer Institute. More information about Clinical Sequencing Evidence-Generating Research can be found at https://cser-consortium.org/. Conceptualization: G.M.C. B.R.K. G.S.B.; Data Curation; K.M.B. M.L.T. C.R.F. S.M.H. D.R.L. M.D.A. J.M.J.L. D.E.G.; Formal Analysis: K.M.B. M.L.T. C.R.F. S.M.H. D.R.L. M.D.A. J.M.J.L. D.E.G. K.M.E. M.E.C. V.G. W.V.K.; Funding Acquisition: G.M.C. B.R.K. G.S.B.; Investigation: K.M.B. M.L.T. C.R.F. S.M.H. D.R.L. M.D.A. J.M.J.L. K.M.E. M.E.C. V.G. W.V.K. D.E.G. S.A.F. H.M. A.C. A.L. K.E.J. L.G.H. H.M.J. M.J. L.A.M. S.L.D. C.T. H.W. K.L. M.B.N.; Methodology: K.M.E. M.E.C. V.G.; Project Administration: K.M.B. M.L.T. C.R.F. K.M.E. M.E.C. V.G. W.V.K. H.M. A.C. A.L. K.E.J. L.G.M. H.M.J. M.J. L.A.M. S.L.D. C.T. H.W. K.L.; Software: J.M.J.L. D.E.G.; Supervision: K.M.B. C.R.F. K.M.E. J.P.-E. A.C.E.H. J.K. W.C. K.B.B. B.M.K. R.S. D.S. S.B.S. S.J.K. G.S.B. B.R.K. G.M.C.; Validation: K.M.E. M.E.C. V.G. W.V.K.; Writing-original draft: K.M.B. M.L.T. C.R.F. J.M.J.L. D.R.L. K.M.E.; Writing-review and editing: K.M.B. M.L.T. C.R.F. S.M.H. D.R.L. J.M.J.L. K.M.E. M.E.C. S.A.F. M.J. J.P.E. A.C.E.H. K.B.B. B.M.K. R.S. S.B.S. S.J.K. G.S.B. B.R.K. G.M.C. All authors declare no competing financial interests in relation to the work described. The review board at the University of Alabama at Birmingham (IRB-300000328) approved and monitored the study. All study participants (parent or legal guardian) were required to give written consent to participate in the study. All individual-level data were de-identified to the research team. The authors received and archived written patient consent to publish individual data. Funding Information: We are grateful to the patients and their families who contributed to this study. We thank the HudsonAlpha Software Development and Informatics team and the Clinical Services Laboratory who contributed to data acquisition and analysis. The SouthSeq project (U01HG007301) was supported by the Clinical Sequencing Evidence-Generating Research consortium , which is funded by the National Human Genome Research Institute with cofunding from the National Institute on Minority Health and Health Disparities and the National Cancer Institute. More information about Clinical Sequencing Evidence-Generating Research can be found at https://cser-consortium.org/ . Publisher Copyright: {\textcopyright} 2021 American College of Medical Genetics and Genomics",
year = "2022",
month = apr,
doi = "10.1016/j.gim.2021.11.020",
language = "English",
volume = "24",
pages = "851--861",
journal = "Genetics in Medicine",
issn = "1098-3600",
number = "4",
}