A productive week in epilepsy genetics. Scientists and editors were certainly busy this week reporting novel variants and deletions as well the experimental and statistical advances for their interpretation.
A de novo GRIN2A missense mutation in early-onset epileptic encephalopathy. We and others have associated variants affecting the GRIN2A gene with a range of childhood focal epilepsy syndromes. Follow the GRIN2A story in the latest edition of Nature Communications where Yuan et al. report a patient with early-onset epileptic encephalopathy. In addition to the clinical data, they provide functional characterization of the identified variant.
Olig1 and interneuron production in developing mammalian brain. Silbereis and colleagues published a study in Neuron last week in which they show that Olig1 represses production of GABAergic interneurons throughout the mouse brain. Abnormal GABAergic interneuron density, and subsequent altered excitatory / inhibitory currents are thought to result in epilepsy.
Automated decision-making process for selecting patients for sequencing. Who should be sequenced in a pedigree? Since genetic analyses are cost intensive, scientists have to carefully consider which patients they want to sequence for family studies. In this weeks edition of The American Journal of Human Genetics Cheung et al. provide a statistical framework for systematic comparison and prioritization for subject-selection choices.
Long-term course of Dravet syndrome. In a recent paper in Epilepsia Takayama and coworkers followed 64 Dravet patients for 11-34 years and compare typical and atypical manifestations of the disease. Most likely, the type of the syndrome influences the long-term course.
Clinical and genomic patients with Phelan-McDermid syndrome. The long-term course of Phelan-McDermid Syndrome, also known as 22q13 deletion syndrome, as well as specific phenotypic features related to specific genetic changes, have not been investigated so far. Sarasua et al. report that seizures were observed three times more frequent in patients affected by de novo deletions of the maternal rather than paternal chromosome 22.
Phenotype and treatment survey of 15q duplication syndrome. Several genomic rearrangements at chromosome 15 are implicated in neurodevelopmental disease including epilepsy. In their study published in Epilepsia Conant et al. examined clinical information of 95 families harboring the 15q duplication. In the analysis they distinguish between idic(15) and int dup(15) duplication types, estimate seizure frequencies and report types of seizures observed in both subgroups.
Deleterious mutation load and population history. In a recent article in Nature genetics Simons et al. use population genetic models to show that that recent human demography has had probably little impact on the average burden of deleterious mutations. Nevertheless, for diseases, which have an effect of reproduction and fitness, mutations of large effect might have an important role and recent growth will have increased their impact.