PT  - JOURNAL ARTICLE
AU  - Hussein Daoud
AU  - Stephanie M. Luco
AU  - Rui Li
AU  - Eric Bareke
AU  - Chandree Beaulieu
AU  - Olga Jarinova
AU  - Nancy Carson
AU  - Sarah M. Nikkel
AU  - Gail E. Graham
AU  - Julie Richer
AU  - Christine Armour
AU  - Dennis E. Bulman
AU  - Pranesh Chakraborty
AU  - Michael Geraghty
AU  - Matthew A. Lines
AU  - Thierry Lacaze-Masmonteil
AU  - Jacek Majewski
AU  - Kym M. Boycott
AU  - David A. Dyment
TI  - Next-generation sequencing for diagnosis of rare diseases in the neonatal intensive care unit
AID  - 10.1503/cmaj.150823
DP  - 2016 Aug 09
TA  - Canadian Medical Association Journal
PG  - E254--E260
VI  - 188
IP  - 11
4099  - http://www.cmaj.ca/content/188/11/E254.short
4100  - http://www.cmaj.ca/content/188/11/E254.full
SO  - CMAJ2016 Aug 09; 188
AB  - Background: Rare diseases often present in the first days and weeks of life and may require complex management in the setting of a neonatal intensive care unit (NICU). Exhaustive consultations and traditional genetic or metabolic investigations are costly and often fail to arrive at a final diagnosis when no recognizable syndrome is suspected. For this pilot project, we assessed the feasibility of next-generation sequencing as a tool to improve the diagnosis of rare diseases in newborns in the NICU.Methods: We retrospectively identified and prospectively recruited newborns and infants admitted to the NICU of the Children’s Hospital of Eastern Ontario and the Ottawa Hospital, General Campus, who had been referred to the medical genetics or metabolics inpatient consult service and had features suggesting an underlying genetic or metabolic condition. DNA from the newborns and parents was enriched for a panel of clinically relevant genes and sequenced on a MiSeq sequencing platform (Illumina Inc.). The data were interpreted with a standard informatics pipeline and reported to care providers, who assessed the importance of genotype–phenotype correlations.Results: Of 20 newborns studied, 8 received a diagnosis on the basis of next-generation sequencing (diagnostic rate 40%). The diagnoses were renal tubular dysgenesis, SCN1A-related encephalopathy syndrome, myotubular myopathy, FTO deficiency syndrome, cranioectodermal dysplasia, congenital myasthenic syndrome, autosomal dominant intellectual disability syndrome type 7 and Denys–Drash syndrome.Interpretation: This pilot study highlighted the potential of next-generation sequencing to deliver molecular diagnoses rapidly with a high success rate. With broader use, this approach has the potential to alter health care delivery in the NICU.