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Will Gene Variant Discovery Explain Fibromyalgia?

  [ 44 votes ]   [ Discuss This Article ] • June 17, 2011

The whole-genome sequencing of 14-year-old California twins with a mystery illness, and of their parents, brother, and grandparents, produced an important discovery with potentially far-reaching implications.

As reported June 15 in Science Translational Medicine(1) and by the National Public Radio Health Blog(2), the twins had a condition termed "DRD" (dopa-responsive dystonia), meaning they had "cerebral palsy-like" spasms thought to result from a deficiency of the neurotransmitter dopamine, which was helped by low doses of the Parkinson’s disease drug L-dopa.

The family’s whole-genome sequencing indicated that the twins had received a double dose of a gene variant (mutation) – one from their father's side, and one from their mother's side – that caused them to have low levels not just of dopamine but of the neurotransmitters serotonin and noradrenalin.

When their neurologist at Children’s Hospital in San Diego decided that in addition to L-dopa they should try supplementing the twins with 5-HTP (5-Hydroxy L-Tryptophan, a precursor that the body uses in serotonin production) their physical condition improved to a remarkable degree. 

Where Does Fibromyalgia Come In?
It turns out that there is a pattern of known fibromyalgia symptoms in the mother’s family (FM affects predominantly females), which could well be linked to the single copy of the gene variant that they carry. The researchers hypothesize that this gene variant could help explain the positive response of some fibromyalgia patients to SSRI anti-depressants, which work by raising serotonin levels.

“If that hypothesis pans out,” the NPR blog comments, “it would suggest that rare genetic disorders such as DRD are just the most dramatic manifestation – in people who inherit a double dose of certain gene variants – of much more common disorders such as fibromyalgia among people who have a single copy of the mutation.”

Discovery Was a Lucky Break

The twins’ father works for a biotech company that makes DNA sequencing machines, and was able to convince the pioneering researchers in whole-genome sequencing at Baylor College of Medicine to take on the family genome-sequencing project.

So is it only a matter of time before they or other cutting edge gene hunters will mount further studies of this potential “fibromyalgia variant” to see what it might reveal?



1. “Whole-Genome Sequencing for Optimized Patient Management,” Matthew Banibridge, et al. Science Translational Medicine, June 15, 2011

2. “Genome Maps Solve Medical Mystery for California Twins,” by Richard Knox. NPR Health Blog, June 16, 2011

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