RT Journal Article
SR Electronic
T1 Next-generation sequencing for diagnosis of rare diseases in the neonatal intensive care unit
JF Canadian Medical Association Journal
JO CMAJ
FD Canadian Medical Association
SP E254
OP E260
DO 10.1503/cmaj.150823
VO 188
IS 11
A1 Hussein Daoud
A1 Stephanie M. Luco
A1 Rui Li
A1 Eric Bareke
A1 Chandree Beaulieu
A1 Olga Jarinova
A1 Nancy Carson
A1 Sarah M. Nikkel
A1 Gail E. Graham
A1 Julie Richer
A1 Christine Armour
A1 Dennis E. Bulman
A1 Pranesh Chakraborty
A1 Michael Geraghty
A1 Matthew A. Lines
A1 Thierry Lacaze-Masmonteil
A1 Jacek Majewski
A1 Kym M. Boycott
A1 David A. Dyment
YR 2016
UL http://www.cmaj.ca/content/188/11/E254.abstract
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.