Twisting DNA and seizures: TDP2 mutations in neurodegeneration with epilepsy

Torsional stress. The DNA double helix has one major problem that we know from telephone cords: it is difficult to untangle. However, our DNA is constantly twisted and untangled for gene transcription. This constant twisting and untwisting produces torsional stress that is relieved by topoisomerases. A recent publication in Nature Genetics now identified a human neurological phenotype that is caused by faulty activity of this mechanism: neurodegeneration with epileptic encephalopathy. However, there are some features of the phenotype that are not easily explained by erroneous DNA twisting. Continue reading

The eye of the tiger, brain iron and the beta-propeller

NBIA. Neurodegeneration with brain iron accumulation (NBIA) is a group of mainly recessive disorders that present with progressive dystonia and dementia. The common feature of these diseases is the excessive accumulation of iron in the basal ganglia. NBIA is very rare and usually not discussed in the context of epilepsy. However, a recent paper in Brain reviews the phenotypes of beta-propeller associated neurodegeneration (BPAN), a novel X-linked disorder with brain iron accumulation. In childhood, the phenotype shares similarities with atypical Rett syndrome and other epileptic encephalopathies, raising the question to what extent the epilepsies that we investigate may be neurodegenerative disorders. Continue reading