Abstracts

Juvenile myoclonic epilepsy (JME) distinguishes from other hereditary generalized epilepsies by age of onset (8-20 years) and the observation of isolated myoclonic jerks that are not necessarily preludes to major tonic clonic seizures. Myoclonia occur characteristically in the morning, soon after awaking, and force the patient to drop object. EEG shows15-30 Hz multispikes and waves complexes. Moreover, 3.5-6 Hz multispike wave complexes sometimes appear in clinically asymptomatic family members (Delgado-Escueta and Enrile-Bascal, 1984). By using 21 families from Mexico, Delgado-Escueta and collaborators (Suzuki et al.2003) encountered a novel gene. This gene encodes a protein whose a domain revealed an EF-hand motif suggesting a role in binding and modulating intracellular calcium.Mutational analysis revealed five missense mutations appearing in epilepsy or EEG spike wave affected members of six unrelated families.
OBJECTIVE :Sleep deprivation, fatigue and alcohol could affect mutations in this gene, decrease calcium binding, increase intracellular calcium concentrations and shift voltage to the depolarizing potentials of epilepsy . Thus, the putative calcium binding activity of the protein coded by this gene should be investigated.
By using quantitative PCR, we first have compared the expression of the transcript of this gene in different tissues. Next, myoclonin protein localisation in HEK-293 cells transfected with EGFP wild type cDNA was used together with Ca2+ imaging after thapsigargin-induced intracellular Ca2+modifications. To study the potential partner(s) of the myoclonin protein, we have realised Yeast two hybrids experiments.
We detected the transcript in various tissues like brain, thymus, kidney, pancreas, liver, heart, lung, spleen, skeletal muscle, stomach with a very high number of copies in testis but also in various cell lines. Increasing intracellular calcium signal leads to a reorganisation of the intracellular distribution of the protein. Morphological results favor a specific role in the control of mitotic process. Identification of some potential partners (still confidential) are in progress.
These data first showed a potential role of a novel fundamental protein implicated in intracellular calcium regulation and / or mitosis in the developpement of the phenotypic aspects of JME.
Delgado-Escueta and Enrile-Bascal, 1984, Neurollogy, 34(3) :285-94
Suzuki et al 2003, American Academy of Neurology, S14.004, Honolulu, Hawaii