Sniffing out the genetic trail

Juvenile myoclonic epilepsy (JME), also known as Janz syndrome, affects, as its name indicates, adolescents and is one of the most common forms of idiopathic generalized epilepsy. If scientists know that genetic factors play a crucial role in the development of this illness, associated with alterations in the cortical architecture, the underlying pathological mechanisms are still widely unrecognised.

At the end of the 1980s a team of researchers discovered the involvement of a region of chromosome 6 in predisposition to JME. In 2002, 2003 and 2004, different teams of scientists placed their fingers on the genes GABRA1, CLCN2 et EFHC1 which, when they mutate, are mixed up in the development of this illness.

Thierry Grisar et Bernard Lakaye, project heads at the ‘Bioenergetics, cerebral excitability and plasticity’ research unit at GIGA-Neurosciences, dug around the functions of the gene EFHC1. Their work has already earned them a first publication (1) on this subject, in the journal Experimental cell research. ‘We used a green fluorescent protein (GFP) to see where the protein issuing from the translation of the EFHC1 gene would go and house itself in the cell,’ explains Bernard Lakaye. ‘This very elementary step allowed us to observe that the protein coded by EFCH1 would not insert itself in the cell membrane, as is the case for the other mutated proteins in JME, but built up within the mitotic spindles of cells in full cell division and within the centrosome, a structure governing the assembly of the cytoskeleton, in resting cells,’ he continues. Apart from this observation, the Liège researchers also wanted to know what the inhibition of this gene implied in terms of cell division. The result: ‘If this gene is not expressed, cell mitosis takes place less well,’ picks up Thierry Grisar.

The first message is thus clear: the EFHC1 protein has something to do with mitosis and when it is absent, this impedes cell division functioning properly.

(1) de Nijs, L., Lakaye, B., Coumans, B., Léon, C., Ikeda, T., Delgado-Escueta, A.V., Grisar, T., Chanas, G., 2006. EFHC1, a protein mutated in juvenile myoclonic epilepsy, associates with the mitotic spindle through its N-terminus. Exp. Cell Res. 312, 2872-2879.