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Science Translational Medicine: New Genetic Test for Severe Childhood Diseases

Doctors could routinely use a new genetic test to screen couples for severe, recessively inherited diseases that they might pass to their offspring, says new research in Science Translational Medicine.

Combined with genetic counseling, this technology may reduce the incidence of severe recessive childhood diseases and help to speed up diagnosis of these disorders in newborns.

“This is the first demonstration that next-generation sequencing is almost ready for use by physicians in routine medical practice,” said lead author Stephen Kingsmore, chief science officer at the National Center for Genome Resources.

“After a decade of hype regarding personalized medicine this is a practical example of the cost-benefit ratio of genome analysis for changing medical practice and reducing the prevalence of severe childhood illnesses.”


Dr. Stephen Kingsmore, Chief Science Officer, National Center for Genome Resources, senior author. | Image © Norah Levine

However, the psychological burden of such a test, along with other issues related to the dynamics of reproduction, will need to be thoroughly addressed before pre-conception carrier screening is made available to the general public, Science Translational Medicine editors note.


Individually, inherited childhood diseases are uncommon in the general population, yet together they account for roughly 20% of all infant deaths and 10% of all pediatric hospitalizations.

In the last few decades, over a thousand genes implicated in these diseases have been identified, yet pre-conception screening for couples in the United States is only recommended for five diseases in specific populations: fragile X syndrome in selected individuals’ cystic fibrosis in Caucasians; and Tay-Sachs disease (along with two others) in individuals of Ashkenazi descent.

Now, Kingsmore and colleagues have developed a pre-conception carrier test capable of screening several hundred DNA samples simultaneously for 448 recessively inherited childhood diseases, a genetic condition that appears only in individuals who have received two copies of a gene, one copy from each parent.

The test is based on a combination of techniques, including target gene capture and enrichment, next generation sequencing and sophisticated bioinformatics analysis. Using the new platform to screen around 100 unrelated individuals, the researchers discovered that on average, each person tested harbored two to three severe childhood disease mutations.

They also discovered that about 10% of disease mutations in commonly used databases are incorrect, suggesting that disease mutation databases need careful scrutiny.

Although the authors acknowledge that their data are preliminary, they point to the apparently random distribution of two to three mutations in the general population as evidence that comprehensive preconception screening should be made available for everyone—not just for a few specific diseases in target groups.

In other words, because most people likely have two to three recessive mutations, they might want to get tested with their partner in case he or she also happens to have the same recessive mutation. That would raise the odds of producing a child with a genetic disorder.

Read the abstract for “New Genetic Test for Severe Childhood Diseases.”

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