Rapid Whole-Genome Sequencing in Neonatal Intensive Care Units – a step forward

Authors

 

Monogenic diseases are frequent causes of neonatal morbidity and mortality, and disease presentations are often undifferentiated at birth. More than 3500 monogenic diseases have been characterized, but clinical testing is available for only some of them and many feature clinical and genetic heterogeneity. Hence, an immense unmet need exists for improved molecular diagnosis in infants. Because disease progression is extremely rapid, albeit heterogeneous, in newborns, molecular diagnoses must occur quickly to be relevant for clinical decision-making.

Here authors describe 50-hour differential diagnosis of genetic disorders by whole-genome sequencing (WGS) that features automated bioinformatic analysis and is intended to be a prototype for use in neonatal intensive care units.

Retrospective 50-hour WGS identified known molecular diagnoses in two children.

Prospective WGS disclosed

– potential molecular diagnosis of a severe GJB2-related skin disease in one neonate;

– BRAT1-related lethal neonatal rigidity and multifocal seizure syndrome in another infant;

– identified BCL9L as a novel, recessive visceral heterotaxy gene (HTX6) in a pedigree; and

– ruled out known candidate genes in one infant.

Sequencing of parents or affected siblings expedited the identification of disease genes in prospective cases.

Thus, rapid WGS can potentially broaden and foreshorten differential diagnosis, resulting in fewer empirical treatments and faster progression to genetic and prognostic counseling.

Source

sciencemag

 

 

 

 

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