DNA Test for Babies Pinpoints Mutations, Speeding Diagnosis
Source: NY Times
By GINA KOLATA
From the day she was born, the girl had seizure after seizure. Doctors at Children’s Mercy Hospital in Kansas City, Mo., frantically tried to keep her alive. Weeks passed and every medication failed. Finally, her family decided to let their baby go, and the medical devices were withdrawn. She was 5 weeks old.
Her doctors suspected a genetic disorder, and as it happened the hospital had just begun a study of a new technique for quickly analyzing the DNA of newborns, zeroing in on mutations that can cause disease.
This new method, published on Wednesday in the magazine Science Translational Medicine, is a proof of concept — a demonstration in four babies that it is possible to quickly scan a baby’s entire DNA and pinpoint a disease-causing mutation in a couple of days instead of the more typical weeks or months.
The study’s investigators said the test could be one of the first practical fruits of the revolution in sequencing an individual’s entire DNA.
FULL story at link.
Read more: http://www.nytimes.com/2012/10/04/health/new-test-of-babies-dna-speeds-diagnosis.html?partner=EXCITE&ei=5043
Research Article: http://stm.sciencemag.org/content/4/154/154ra135
Diagnostics
Rapid Whole-Genome Sequencing for Genetic Disease Diagnosis in Neonatal Intensive Care Units
Carol Jean Saunders1,2,3,4,5,*,
Neil Andrew Miller1,2,4,*,
Sarah Elizabeth Soden1,2,4,*,
Darrell Lee Dinwiddie1,2,3,4,5,*,
Aaron Noll1,
Noor Abu Alnadi4,
Nevene Andraws3,
Melanie LeAnn Patterson1,3,
Lisa Ann Krivohlavek1,3,
Joel Fellis6,
Sean Humphray6,
Peter Saffrey6,
Zoya Kingsbury6,
Jacqueline Claire Weir6,
Jason Betley6,
Russell James Grocock6,
Elliott Harrison Margulies6,
Emily Gwendolyn Farrow1,
Michael Artman2,4,
Nicole Pauline Safina1,4,
Joshua Erin Petrikin2,3,
Kevin Peter Hall6 and
Stephen Francis Kingsmore1,2,3,4,5,†
+ Author Affiliations
1Center for Pediatric Genomic Medicine, Children’s Mercy Hospital, Kansas City, MO 64108, USA.
2Department of Pediatrics, Children’s Mercy Hospital, Kansas City, MO 64108, USA.
3Department of Pathology, Children’s Mercy Hospital, Kansas City, MO 64108, USA.
4School of Medicine, University of Missouri-Kansas City, Kansas City, MO 64108, USA.
5University of Kansas Medical Center, Kansas City, KS 66160, USA.
6Illumina Inc., Chesterford Research Park, Little Chesterford, CB10 1XL Essex, UK.
+ Author Notes
↵* These authors contributed equally to this work.
↵†To whom correspondence should be addressed. E-mail: sfkingsmore@cmh.edu
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.
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