Editorial

In this issue ofBrain David Brenner and colleagues report a hot-spot of mutations in the kinesin family geneKIF5A causing familial amyotrophic lateral sclerosis, adding to the existing genetic evidence implicating altered cytoskeletal function and intracellular transport in this disease. Two other papers broaden the range of manifestations of genetic disorders involving glutamate receptors. Juliette Piard, George Umanah, Frederike Harms and co-workers identify a mutation in the AAA+ family ATPase Thorase, encoded byATAD1, which leads to lethal encephalopathy and arthrogryposis, while Andrew Fry, Katherine Fawcett and colleagues report an association betweende novo mutations ofGRIN1, which codes for the GluN1 subunit of NMDA receptors, and extensive bilateral polymicrogyria, with several probands presenting with developmental delay, microcephaly, visual impairment or refractory epilepsy. The association between NMDA receptors and abnormalities of cortical development is especially intriguing, because previous reports onGRIN1 mutations have only identified relatively minor structural abnormalities in association with various levels of intellectual disability, epilepsy or movement disorders. Some of the polymicrogyria-associated mutations were shown to confer a gain of function, providing a tentative link to animal studies that have used NMDA receptor agonists to induce cortical malformations.

Source: Brain - February 27, 2018 Category: Neurology Source Type: research