Targeted gene panel sequencing for the rapid diagnosis of acutely ill infants. Issue 7 (13th June 2019)

• Record Type: Journal Article
• Authors: Brunelli, Luca; Jenkins, Sabrina M.; Gudgeon, James M.; Bleyl, Steven B.; Miller, Christine E.; Tvrdik, Tatiana; Dames, Shale A.; Ostrander, Betsy; Daboub, Josue A. F.; Zielinski, Brandon A.; Zinkhan, Erin K.; Underhill, Hunter R.; Wilson, Theodore; Bonkowsky, Joshua L.; Yost, Christian C.; Botto, Lorenzo D.; Jenkins, Justin; Pysher, Theodore J.; Bayrak‐Toydemir, Pinar; Mao, Rong
• Is Part Of: Molecular genetics & genomic medicine. Volume 7:Issue 7(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-06-13
• Subjects: genetic diagnosis -- neonatology -- newborn -- precision medicine -- rapid sequencing; Medical genetics -- Periodicals; Genomics -- Periodicals; 616.042
• DOI: 10.1002/mgg3.796
• Languages: English
• ISSNs: 2324-9269

Abstract

Abstract: 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. Abstract : 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 in the NICU/PICU/CICU. This study shows for the first time that rapid sequencing of a panel that includes the majority of known disease‐causing genes has a diagnostic yield similar to previously published rates for rapid exome and genome sequencing. Early diagnosis appeared to have a positive impact on clinical management.