Whole-genome sequencing for optimized patient management.

TitleWhole-genome sequencing for optimized patient management.
Publication TypeJournal Article
Year of Publication2011
AuthorsBainbridge, MN, Wiszniewski, W, Murdock, DR, Friedman, J, Gonzaga-Jauregui, C, Newsham, I, Reid, JG, Fink, JK, Morgan, MB, Gingras, M-C, Muzny, DM, Hoang, LD, Yousaf, S, Lupski, JR, Gibbs, RA
JournalSci Transl Med
Date Published2011 Jun 15
KeywordsAdolescent, Decision Making, Dystonic Disorders, Female, Genome, Human, Humans, Levodopa, Male, Patient Care, Pedigree, Sequence Analysis, DNA, Treatment Outcome, Twins, Dizygotic

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.

Alternate JournalSci Transl Med
PubMed ID21677200
PubMed Central IDPMC3314311
Grant ListR01 NS069700-01A1 / NS / NINDS NIH HHS / United States
U54 HG003273 / HG / NHGRI NIH HHS / United States
R01 NS069700 / NS / NINDS NIH HHS / United States
R01 NS058529 / NS / NINDS NIH HHS / United States
5 U54 HG003273 / HG / NHGRI NIH HHS / United States

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