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Whole-Genome Sequencing for Optimized Patient Management

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Science Translational Medicine  15 Jun 2011:
Vol. 3, Issue 87, pp. 87re3
DOI: 10.1126/scitranslmed.3002243

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Guiding Treatment with Genomics

Whole-genome sequencing of DNA from patients with different diseases is proving useful for identifying new disease-causing mutations, but can it help physicians make better decisions about treatment options for these patients? A new study by Bainbridge and colleagues suggests that it can. Bainbridge et al. sequenced the complete genomes of a male and female fraternal twin pair, who had been diagnosed 9 years earlier with the movement disorder dopa (3,4-dihydroxyphenylalanine)–responsive dystonia (DRD). This complex disorder is difficult to diagnose and may be mistaken for other movement disorders involving loss of the neurotransmitter dopamine. The standard treatment for DRD is to replace dopamine by providing a dopamine precursor called l-dopa, the drug that is also used to treat the common movement disorder Parkinson disease. When the twins were diagnosed with DRD, they seemed to fit the classic description of DRD and were given l-dopa, which did help to alleviate many of their symptoms. When Bainbridge and colleagues analyzed the full genome sequences of the twins, they were surprised to discover no mutations in the two genes most commonly mutated in DRD. Instead, they pinpointed a mutation in the SPR gene encoding sepiapterin reductase, which synthesizes a cofactor needed for the action of enzymes that make not only dopamine but also the neurotransmitter serotonin. This finding suggested to the authors that supplementing the twin’s current l-dopa treatment with a serotonin precursor, 5-hydroxytryptophan, might provide further improvement in their symptoms. Sure enough, when the twins were given both l-dopa and 5-hydroxytryptophan instead of l-dopa alone, they showed improvement in their symptoms after 1 to 2 weeks, including greater attention in school, better motion and coordination, and reduced hand tremor as evidenced by more legible handwriting. Although this study involved only one twin pair, it does demonstrate how whole-genome sequencing could be applied to glean more detailed information about a patient’s disease, leading to more optimized treatment and a better outcome.


  • Citation: M. N. Bainbridge, W. Wiszniewski, D. R. Murdock, J. Friedman, C. Gonzaga-Jauregui, I. Newsham, J. G. Reid, J. K. Fink, M. B. Morgan, M.-C. Gingras, D. M. Muzny, L. D. Hoang, S. Yousaf, J. R. Lupski, R. A. Gibbs, Whole-Genome Sequencing for Optimized Patient Management. Sci. Transl. Med. 3, 87re3 (2011).

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