TY - JOUR
T1 - Whole-genome sequencing for optimized patient management
AU - Bainbridge, Matthew N.
AU - Wiszniewski, Wojciech
AU - Murdock, David R.
AU - Friedman, Jennifer
AU - Gonzaga-Jauregui, Claudia
AU - Newsham, Irene
AU - Reid, Jeffrey G.
AU - Fink, John K.
AU - Morgan, Margaret B.
AU - Gingras, Marie Claude
AU - Muzny, Donna M.
AU - Hoang, Linh D.
AU - Yousaf, Shahed
AU - Lupski, James R.
AU - Gibbs, Richard A.
PY - 2011/6/15
Y1 - 2011/6/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=79959316645&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79959316645&partnerID=8YFLogxK
U2 - 10.1126/scitranslmed.3002243
DO - 10.1126/scitranslmed.3002243
M3 - Article
C2 - 21677200
AN - SCOPUS:79959316645
SN - 1946-6234
VL - 3
JO - Science translational medicine
JF - Science translational medicine
IS - 87
M1 - 87re3
ER -