Translation of genetic findings to clinical practice in juvenile myoclonic epilepsy

Abstract

It has been estimated that JME (juvenile myoclonic epilepsy), when compared to other adult epilepsy syndromes, is most likely to have a genetic cause. However, decades of research have not brought us closer to finding a single 'JME gene' that is important on a population basis. Is this due in part to the genetic complexity of the syndrome, the cryptic nature of the genes of effect, or perhaps because JME is not one condition at all but many? Before we can begin to harness the power of next-generation sequencing techniques, we must first reduce JME down to lacunae of homogeneity--using increasingly more sophisticated phenotyping tools. The current technological advances in gene sequencing have been used to dramatic effect to identify single gene causes in rare syndromes and identify risk variants in malignancies. Filtering the variety of the human exome or genome down into a handful of biologically plausible candidates now relies on a pipeline of biostatistics, software, and functional analyses. It is simply unacceptable to return uncertain findings to the clinical domain and, therefore, it is crucial that pathogenicity is fully determined before families receive genetic counseling and test results.