TY - JOUR
T1 - Targeted gene panel sequencing for the rapid diagnosis of acutely ill infants
AU - Brunelli, Luca
AU - Jenkins, Sabrina M.
AU - Gudgeon, James M.
AU - Bleyl, Steven B.
AU - Miller, Christine E.
AU - Tvrdik, Tatiana
AU - Dames, Shale A.
AU - Ostrander, Betsy
AU - Daboub, Josue A.F.
AU - Zielinski, Brandon A.
AU - Zinkhan, Erin K.
AU - Underhill, Hunter R.
AU - Wilson, Theodore
AU - Bonkowsky, Joshua L.
AU - Yost, Christian C.
AU - Botto, Lorenzo D.
AU - Jenkins, Justin
AU - Pysher, Theodore J.
AU - Bayrak-Toydemir, Pinar
AU - Mao, Rong
N1 - Publisher Copyright:
© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.
PY - 2019/7
Y1 - 2019/7
N2 - Background: Exome/genome sequencing (ES/GS) have been recently used in neonatal and pediatric/cardiac intensive care units (NICU and PICU/CICU) to diagnose and care for acutely ill infants, but the effectiveness of targeted gene panels for these purposes remains unknown. Methods: RapSeq, a newly developed panel targeting 4,503 disease-causing genes, was employed on selected patients in our NICU/PICU/CICU. Twenty trios were sequenced from October 2015 to March 2017. We assessed diagnostic yield, turnaround times, and clinical consequences. Results: A diagnosis was made in 10/20 neonates (50%); eight had de novo variants (ASXL1, CHD, FBN1, KMT2D, FANCB, FLNA, PAX3), one was a compound heterozygote for CHAT, and one had a maternally inherited GNAS variant. Preliminary reports were generated by 9.6 days (mean); final reports after Sanger sequencing at 16.3 days (mean). In all positive infants, the diagnosis changed management. In a case with congenital myasthenia, diagnosis and treatment occurred at 17 days versus 7 months in a historical control. Conclusions: This study shows that a gene panel that includes the majority of known disease-causing genes can rapidly identify a diagnosis in a large number of tested infants. Due to simpler deployment and interpretation and lower costs, this approach might represent an alternative to ES/GS in the NICU/PICU/CICU.
AB - Background: Exome/genome sequencing (ES/GS) have been recently used in neonatal and pediatric/cardiac intensive care units (NICU and PICU/CICU) to diagnose and care for acutely ill infants, but the effectiveness of targeted gene panels for these purposes remains unknown. Methods: RapSeq, a newly developed panel targeting 4,503 disease-causing genes, was employed on selected patients in our NICU/PICU/CICU. Twenty trios were sequenced from October 2015 to March 2017. We assessed diagnostic yield, turnaround times, and clinical consequences. Results: A diagnosis was made in 10/20 neonates (50%); eight had de novo variants (ASXL1, CHD, FBN1, KMT2D, FANCB, FLNA, PAX3), one was a compound heterozygote for CHAT, and one had a maternally inherited GNAS variant. Preliminary reports were generated by 9.6 days (mean); final reports after Sanger sequencing at 16.3 days (mean). In all positive infants, the diagnosis changed management. In a case with congenital myasthenia, diagnosis and treatment occurred at 17 days versus 7 months in a historical control. Conclusions: This study shows that a gene panel that includes the majority of known disease-causing genes can rapidly identify a diagnosis in a large number of tested infants. Due to simpler deployment and interpretation and lower costs, this approach might represent an alternative to ES/GS in the NICU/PICU/CICU.
KW - genetic diagnosis
KW - neonatology
KW - newborn
KW - precision medicine
KW - rapid sequencing
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U2 - 10.1002/mgg3.796
DO - 10.1002/mgg3.796
M3 - Article
C2 - 31192527
AN - SCOPUS:85068915324
SN - 2324-9269
VL - 7
JO - Molecular Genetics and Genomic Medicine
JF - Molecular Genetics and Genomic Medicine
IS - 7
M1 - e00796
ER -