Imbalance of a rare second messenger – FIG4 mutations in polymicrogyria

Brain malformations. Various brain malformations are thought to have a genetic basis, and several genes have already been identified. Polymicrogyria is a particular form of congenital brain malformation due to an excessive number of small and sometimes malformed gyri. In a recent publication in Neurology, mutations in FIG4 are described in a familial form of polymicrogyria. However, the FIG4 gene is no stranger in the field of neurogenetics. Continue reading

TBC1D24, DOORS Syndrome, and the unexpected heterogeneity of recessive epilepsies

The return of TBC1D24. In 2010, the TBC1D24 gene was the first gene for human epilepsies to be discovered through next generation sequencing techniques. Ever since, this gene has been a mystery, as the phenotypes of the families with recessive mutations in this gene varied widely. Now, a recent paper in Lancet Neurology finds recessive TBC1D24 mutations in a large proportion of patients with DOORS syndrome, a rare distinct autosomal recessive syndrome with deafness, onychodystrophy, osteodystrophy, intellectual disability (mental retardation), and seizures. This finding demonstrates that we have only just scratched the surface of the complicated genetic architecture of human epilepsies. Continue reading