期刊
SCIENCE TRANSLATIONAL MEDICINE
卷 3, 期 87, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scitranslmed.3002243
关键词
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资金
- Life Technologies and National Human Genome Research Institute (NHGRI)
- NHGRI [5 U54 HG003273]
- National Institute of Neurological Disorders and Stroke [R01 NS058529]
- Natural Sciences and Engineering Research Council of Canada
- Department of Veterans Affair
- NIH [R01 NS069700]
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 neuro-transmitters dopamine and serotonin. Supplementation of L-dopa therapy with 5-hydroxytryptophan, a serotonin precursor, resulted in clinical improvements in both twins.
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