Science paper describes FUS missense mutation linked to ALS6 and motor neurons.
A collaboration of scientists led by the Northwestern University Feinberg School of Medicine has found a new gene whose mutations reportedly cause 5% of inherited cases of ALS.
The researchers identified a missense mutation in the gene encoding fused in sarcoma (FUS) in a British kindred linked to ALS6. Earlier research by the colleagues extended the genetic knowledge of familial ALS by identifying the first and second ALS genes (SOD1 and ALSIN) in addition to identifying loci on chromosomes 9, 15, 16, and X.
The team identified two other missense mutations in eight families as part of a survey of 197 familial ALS index cases. Postmortem analysis of three FUS mutation cases showed FUS-immunoreactive cytoplasmic inclusions and mostly lower motor neuron degeneration.
Cellular expression studies revealed aberrant localization of mutant FUS protein. FUS is involved in the regulation of transcription and RNA splicing and transport, and it has functional homology to another ALS gene, TARDBP. This suggests that a common mechanism may underlie motor neuron degeneration.
The article is published February 27 in Science.