Beyond recessive – KCNC1 mutations in progressive myoclonus epilepsy

PME. The progressive myoclonus epilepsies (PME) are a particular subtype of seizure disorders characterized by progressive myoclonus, generalized seizures and cognitive deterioration. Known causes of PME include recessive mutations in several well-known genes, but the genetic cause is unknown in a significant proportion of patients. Now, in a recent paper in Nature Genetics, de novo mutations in KCNC1 are identified as a novel cause of progressive myoclonus epilepsies. In addition to elucidating the genetic basis in a significant subset of patients with PME, the authors demonstrate that de novo mutations play an important role in a group of diseases usually thought to be recessive. Continue reading

C9orf72 expansions and neurodegenerative disease

Out of my league. I must admit that I know very little about the genetics of neurodegenerative disorders, but a recent article in the American Journal of Human Genetics caught my interest. Massive expansions of a hexanucleotide repeat in the first intron of C9orf72 are a known cause of frontotemporal lobar degeneration (FTLD)  and Amyotrophic Lateral Sclerosis (ALS). With a novel method for rapid screening for these expansions, the authors investigate a large cohort of patients with neurodegenerative disorders and population controls, providing an interesting example of how seemingly clear-cut monogenic disorders acquire an unanticipated degree of complexity. Continue reading