Mutations in BICD2 cause autosomal dominant SMA

A new gene, bicaudal D homolog 2 (Drosophila) (BICD2) has been identified to cause both dominant congenital spinal muscular atrophy (DCSMA) and hereditary spastic paraplegia (HSP). Spinal muscular atrophy (SMA) is a heterogeneous group of neuromuscular disorders caused by degeneration of lower motor neurons. Although functional loss of SMN1 is associated with autosomal-recessive childhood SMA, the genetic cause for most families affected by dominantly inherited SMA is unknown. Dominant CSMA shows clinical overlap with hereditary spastic paraplegia (HSP), a lower-limb-predominant disorder of corticospinal motor neurons that develops in childhood or adult life. The importance of BICD2 for motor neurons is underlined by the simultaneous publication of the same gene causing DCSMA by three different groups of researchers, in the same issue of the American Journal of Human Genetics. Overall, the findings from the three groups provide insight into the mechanism underlying both the static and the slowly progressive clinical features and the motor neuron pathology that characterise BICD2-associated diseases, and highlight the importance of the dynein-dynactin transport pathway in the development and survival of both lower and upper motor neurons.