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 journalArticle

195 Citations (Scopus)

Abstract

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
Volume3
Issue number87
DOIs
StatePublished - Jun 15 2011
Externally publishedYes

Fingerprint

Levodopa
Genome
sepiapterin reductase
Neurotransmitter Agents
Dopamine
Serotonin
Dizygotic Twins
5-Hydroxytryptophan
Dihydroxyphenylalanine
Dystonia
Movement Disorders
Mixed Function Oxygenases
DNA Sequence Analysis
Mutation
Enzymes
Therapeutics
Genes
sapropterin

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Bainbridge, M. N., Wiszniewski, W., Murdock, D. R., Friedman, J., Gonzaga-Jauregui, C., Newsham, I., ... Gibbs, R. A. (2011). Whole-genome sequencing for optimized patient management. Science Translational Medicine, 3(87), [87re3]. https://doi.org/10.1126/scitranslmed.3002243

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

In: Science Translational Medicine, Vol. 3, No. 87, 87re3, 15.06.2011.

Research output: Contribution to journalArticle

Bainbridge, MN, Wiszniewski, W, Murdock, DR, Friedman, J, Gonzaga-Jauregui, C, Newsham, I, Reid, JG, Fink, JK, Morgan, MB, Gingras, MC, Muzny, DM, Hoang, LD, Yousaf, S, Lupski, JR & Gibbs, RA 2011, 'Whole-genome sequencing for optimized patient management', Science Translational Medicine, vol. 3, no. 87, 87re3. https://doi.org/10.1126/scitranslmed.3002243
Bainbridge MN, Wiszniewski W, Murdock DR, Friedman J, Gonzaga-Jauregui C, Newsham I et al. Whole-genome sequencing for optimized patient management. Science Translational Medicine. 2011 Jun 15;3(87). 87re3. https://doi.org/10.1126/scitranslmed.3002243
Bainbridge, Matthew N. ; Wiszniewski, Wojciech ; Murdock, David R. ; Friedman, Jennifer ; Gonzaga-Jauregui, Claudia ; Newsham, Irene ; Reid, Jeffrey G. ; Fink, John K. ; Morgan, Margaret B. ; Gingras, Marie Claude ; Muzny, Donna M. ; Hoang, Linh D. ; Yousaf, Shahed ; Lupski, James R. ; Gibbs, Richard A. / Whole-genome sequencing for optimized patient management. In: Science Translational Medicine. 2011 ; Vol. 3, No. 87.
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