Targeted gene panel sequencing for the rapid diagnosis of acutely ill infants

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 licence: CC BY-NC-ND

1. 13.

   OMIM.org: Online Mendelian Inheritance in Man (OMIM®), an online catalog of human genes and genetic disorders · 2014

2. 14.

   Clinical sequencing: is WGS the better WES? · 2016

3. 21.

   Rapid whole-genome sequencing decreases infant morbidity and cost of hospitalization · 2018

4. 25.

   The NSIGHT1-randomized controlled trial: rapid whole-genome sequencing for accelerated etiologic diagnosis in critically ill infants · 2018

22 more references, whose wording the paper’s licence keeps private.

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.