Whole-genome sequencing for optimized patient management

Matthew N. Bainbridge, Wojciech Wiszniewski, David R. Murdock, Jennifer Friedman, Claudia Gonzaga-Jauregui, Irene Newsham, Jeffrey G. Reid, John K. Fink, Margaret B. Morgan, Marie Claude Gingras, Donna M. Muzny, Linh D. Hoang, Shahed Yousaf, James R. Lupski, Richard A. Gibbs

Research output: Contribution to journalArticlepeer-review

234 Scopus citations


Whole-genome sequencing of patient DNA can facilitate diagnosis of a disease, but its potential for guiding treatment has been under-realized. We interrogated the complete genome sequences of a 14-year-old fraternal twin pair diagnosed with dopa (3,4-dihydroxyphenylalanine)-responsive dystonia (DRD; Mendelian Inheritance in Man #128230). DRD is a genetically heterogeneous and clinically complex movement disorder that is usually treated with L-dopa, a precursor of the neurotransmitter dopamine. Whole-genome sequencing identified compound heterozygous mutations in the SPR gene encoding sepiapterin reductase. Disruption of SPR causes a decrease in tetrahydrobiopterin, a cofactor required for the hydroxylase enzymes that synthesize the neurotransmitters dopamine and serotonin. Supplementation of L-dopa therapy with 5-hydroxytryptophan, a serotonin precursor, resulted in clinical improvements in both twins.

Original languageEnglish (US)
Article number87re3
JournalScience translational medicine
Issue number87
StatePublished - Jun 15 2011
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)


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