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Synaptic vesicles play a key role in this process, as they are stored in the presynaptic compartment and release their content by exocytosis in the synaptic cleft.Endocytosis and recycling of synaptic vesicle membranes allow their reuse in multiple cycles of secretion, hence maintain the synapse function during high frequency stimulation (Sudhof, 2004).

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This study was a combined effort of the Euro EPINOMICS RES consortium working group on recessive epilepsies, a project on presumed mitochondrial diseases from La Pitié-Salpêtrière Hôpital in Paris, and the medical genetics unit of the Children’s Hospitals and Clinics of Minnesota.

The study was approved by the Ethical Committees of the local institutes.

EEG showed a modified hypsarrhythmia or multifocal epileptic activity on a slow background, whereas brain MRI was normal. This family was included in a project of the Euro EPINOMICS RES consortium that studied five consanguineous and 17 non-consanguineous families with at least two siblings presenting with unexplained early onset seizures and intellectual disability. All parents are healthy, affected children are indicated by filled symbols.

Overall, both children showed a neurodegenerative disease course with a progressive spastic quadriplegia, severe intellectual disability, central visual impairment, and progressive feeding problems for which tube feeding was started around the age of 5 years. Double horizontal lines indicate consanguinity between the parents and arrows point towards the patients whose fibroblasts were used in the m RNA expression studies.

(B) Visualization of sequencing reads produced by direct Sanger sequencing during variant validation.