A Clinical Option

Technology Review reports on the movement of sequencing into the clinic for children with rare diseases.

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The identification of genes

The identification of genes that are functionally aberrant in rare diseases can on occasion be very useful for understanding how certain common pathologies might develop. However, this is generally impractical for the diagnoses of common diseases in the general population where most health care costs are borne. A small number of highly publicized cases of genome-wide sequencing studies have been used to drive a DNA sequencing agenda for the diagnosis and treatment of human diseases with very dubious cost-benefit value.

With Nicholas Volker's genome, the Wisconsin researchers identified a mutation on his X-chromosome that was linked to another case of an individual that had an inherited immune disorder. However, it was not established that this mutation actually produces an immune disorder. Moreover, it is unclear that even with a causal link to the responsible gene that this knowledge could lead to an effective treatment.

The Wisconsin team had previously performed over 100 surgeries on Nicholas Volker and already had evidence that he had an immune disorder. The umbilical cord-blood transplant of stem cells was already a potential therapy. Regardless of the results of the genome wide sequencing that was performed on Nicholas Volker's DNA, it would seem that this was the only viable option left. Therefore, it does not seem that the extra genomic analysis was truly pivotal in this case.

With the dramatic reduction in direct genome-wide sequencing costs, it may make sense to perform such genetic analyses on rare diseases to build up databases on different mutations that might cause various pathologies. However, in the near future, this will most likely not be particularly helpful to those unfortunate people that are afflicted with these diseases. The real cost for disease diagnosis by gene-wide sequencing will really come from the labour involved in the analyses of the DNA sequence data, including sorting through some 50 million possible mutations and common genetic variations that will have nothing to do with the manifested disease in the patient. The frustration will come when it is realized that there still is not much that can be done for most of these rare diseases without further research and development into these illnesses.

High penetrance rare genetic

High penetrance rare genetic disorders play a disproprotionately important role in pediatric medicine. Simply having a molecular diagnosis can in some case head off much more expensive traditional and unnecessary diagnostic tests. In some cases, a molecular diagnosis does have implications for better patient management. I agree that the practical value of genetics for diagnosing and treating common, late onset degenerative diseases is still debatable. But the world of pediatrics is quite different from adult medicine.

Indeed, the benefit of

Indeed, the benefit of identifying what treatments _won't_ work has both economic and palliative value.