Gene Hunters Find Cause of Rare Movement Disorder

In a published article from HHMI, professor of neurology at the University of California San Francisco Louis Ptáček announced that an international team of scientists have pinpointed the gene responsible for a rare disease known as dyskinesia that causes seizures in infancy and sudden, uncontrollable movements in adolescence and early adulthood.

This article is brief but consists of many provocative details.  Dr. Ptáček first encountered dyskinesia in a fifteen year old patient when he was a medical student.  Spending laborious time in the medical library, Ptáček figured out the diagnosis: paroxysmal kinesigenic dyskinesia, or PKD, which was very rare and had only a handful of documented cases.  PKD was documented to be treatable with a low dose of a common anticonvulsant medication.  When doctors gave the boy the drug, carbamazepine, improvements were apparent.

Ptáček has been studying rare movement disorders ever since.  Again, the interesting detail of this article is the actual laboratory techniques to identify the genetic sequence responsible for the disease state of PKD.  For PKD, scientists attempted to use gene mapping based on recombination frequencies to pinpoint the location of the PKD gene using genetic markers.  This technique, however, has its limitations, particularly in the PKD gene since the gene is located near the centromere, where very little recombination occurs.

The scientists collectively consisting of two dozen institutions in 10 countries therefore combined their their samples and performed whole-genome sequencing of 6 billion DNA letters.  The teams analyzed the DNA of one member of each of the six most well-characterized families with PKD/IC.  All six carried mutations in a gene called PRRT2.  In a later analysis, the researchers found the same PRRT2 mutations in 24 of the 25 known PKD/IC families.  To me, it is amazing to read that scientists would go through such great lengths to identify the genetic causation of a disease state, and that such a search, at least from one scientist's point of view, principally starts with an interaction with an afflicted patient.

One of the biggest mysteries about PKD/IC, which is that for some individuals, symptoms completely disappear by middle age.  The identification of the PKD gene is a meaningful step in discovering further secrets not just of this particular gene, but the complex interface between genotype and phenotype in higher-level organisms.

[caption id="attachment_3753" align="aligncenter" width="686" caption="The first printout of the human genome to be presented as a series of books, displayed at the Wellcome Collection, London."][/caption]