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Sci Transl Med. 2011 Jun 15;3(87):87re3. doi: 10.1126/scitranslmed.3002243.

Whole-genome sequencing for optimized patient management.

Author information

1
Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.

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.

PMID:
21677200
PMCID:
PMC3314311
DOI:
10.1126/scitranslmed.3002243
[Indexed for MEDLINE]
Free PMC Article

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