NEW YORK (GenomeWeb) – In Nature Genetics, an international team led by investigators at the University of Helsinki described the recurrent mutation that it detected in more than 10 percent of the progressive myoclonus epilepsy cases it considered.
In their original search for genetic contributors to the rare, inherited condition, the researchers did exome sequencing on 84 unrelated individuals affected with PME, a particularly severe form of epilepsy that involves not only seizures, but also progressive neurological decline. Fourteen individuals came from families prone to PME, while the remaining 70 cases were sporadic.
The search uncovered a de novo mutation that was present at the same site in a potassium ion channel-coding gene called KCNC1 in 11 of the original exomes — results the team verified using Sanger sequencing.
When they did targeted testing on another 28 individuals with PME, the investigators found that some 7 percent of that group carried a heterozygous version of the KCNC1 glitch, though no other alterations in the gene turned up in the exome sequencing data. Their follow-up experiments indicated that the newly identified change has a dominant-negative effect, leading to a loss of KCNC1 function.
The analysis also uncovered several examples of mutations affecting genes with known or suspected ties to PME or other forms of epilepsy, the study's authors noted, though the "genetic basis of disease remained unknown in over two-thirds of the cases."
"In light of de novo mutations being established as an important cause of PME," they wrote, "exome sequencing in a family trio setting could be pursued to further dissect this heterogeneous cohort."