Journal article
Rapid Whole-Genome Sequencing for Genetic Disease Diagnosis in Neonatal Intensive Care Units
Science translational medicine, Vol.4(154), pp.154ra135-154ra135
10/03/2012
DOI: 10.1126/scitranslmed.3004041
PMCID: PMC4283791
PMID: 23035047
Abstract
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. We 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.
Details
- Title: Subtitle
- Rapid Whole-Genome Sequencing for Genetic Disease Diagnosis in Neonatal Intensive Care Units
- Creators
- Carol Jean Saunders - Children's Mercy HospitalNeil Andrew Miller - Children's Mercy HospitalSarah Elizabeth Soden - University of Missouri–Kansas CityDarrell Lee Dinwiddie - Children's Mercy HospitalAaron Noll - Children's Mercy HospitalNoor Abu Alnadi - University of Missouri–Kansas CityNevene Andraws - Children's Mercy HospitalMelanie LeAnn Patterson - Children's Mercy HospitalLisa Ann Krivohlavek - Children's Mercy HospitalJoel Fellis - Illumina Inc., Chesterford Research Park, Little Chesterford, CB10 1XL Essex, UK.Sean Humphray - Illumina Inc., Chesterford Research Park, Little Chesterford, CB10 1XL Essex, UK.Peter Saffrey - Illumina Inc., Chesterford Research Park, Little Chesterford, CB10 1XL Essex, UK.Zoya Kingsbury - Illumina Inc., Chesterford Research Park, Little Chesterford, CB10 1XL Essex, UK.Jacqueline Claire Weir - Illumina Inc., Chesterford Research Park, Little Chesterford, CB10 1XL Essex, UK.Jason Betley - Illumina Inc., Chesterford Research Park, Little Chesterford, CB10 1XL Essex, UK.Russell James Grocock - Illumina Inc., Chesterford Research Park, Little Chesterford, CB10 1XL Essex, UK.Elliott Harrison Margulies - IlluminaEmily Gwendolyn Farrow - Children's Mercy HospitalMichael Artman - Children's Mercy HospitalNicole Pauline Safina - University of Missouri–Kansas CityJoshua Erin Petrikin - Children's Mercy HospitalKevin Peter Hall - Illumina Inc., Chesterford Research Park, Little Chesterford, CB10 1XL Essex, UK.Stephen Francis Kingsmore - Children's Mercy Hospital
- Resource Type
- Journal article
- Publication Details
- Science translational medicine, Vol.4(154), pp.154ra135-154ra135
- Publisher
- Amer Assoc Advancement Science
- DOI
- 10.1126/scitranslmed.3004041
- PMID
- 23035047
- PMCID
- PMC4283791
- ISSN
- 1946-6234
- eISSN
- 1946-6242
- Number of pages
- 13
- Grant note
- U19HD077693 / EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) Children's Mercy Hospital Marion Merrell Dow Foundation Illumina Inc.
- Language
- English
- Date published
- 10/03/2012
- Academic Unit
- Stead Family Department of Pediatrics; Medical Genetics and Genomics
- Record Identifier
- 9984354147102771
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