Whole-genome sequencing for optimized patient management

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Decision Making
  • Dystonic Disorders* / drug therapy
  • Dystonic Disorders* / genetics
  • Female
  • Genome, Human*
  • Humans
  • Levodopa / therapeutic use
  • Male
  • Patient Care*
  • Pedigree
  • Sequence Analysis, DNA*
  • Treatment Outcome
  • Twins, Dizygotic / genetics


  • Levodopa

Supplementary concepts

  • Dystonia, Dopa-responsive