FUS mutation can lead to Juvenile ALS

A study focusing on juvenile ALS (JALS) was published in the January 16 online issue of Archives of Neurology. This study was conducted by a team of Montreal researchers: VeroniqueBelzil, MSc; Jean-Sébastien Langlais, MD, MSc; Hussein Daoud, PhD; Patrick Dion, PhD; Bernard Brais, MD; and Guy Rouleau, MD, PhD. The team sequenced all the coding exons of SOD1, TARDBP, and FUS from a 19-year-old patient who has JALS with a rapid course of clinical progression.

JALS is generally associated with slow disease progression, with neurodegeneration beginning before the age of 25. Research in the past has shown that a number of genes may be responsible in causing JALS. Mutations in the ALSIN gene caused JALS type 2 (ALS2), as well as juvenile primary lateral sclerosis, and infantile-onset ascending spastic paralysis. Mutations in SETX gene are strongly associated with JALS. On the other hand, mutations in the SOD1, TARDBP, and FUS genes typically cause pure ALS, with onset between 46 and 56 years of age. However, recent studies showed that a few mutations in FUS are associated with juvenile-onset of ALS that has very rapid progression.

The researchers found a novel 1-base pair deletion in exon 14 of the FUS gene which led to a frameshift and integration of 33 new amino acids. The variant p.R495QfsX527 was located in the conserved, extreme C terminal of the FUS protein. This variant was also identified in the unaffected 47-year-old mother of the patient who showed no signs of the disease. The researchers concluded that FUS mutation can lead to an early-onset “malignant” form of ALS. Data from the study also showed that disruption of the conserved C terminal of FUS is critical for the development of ALS.

For more information on the JALS study, please visit 
http://archneur.ama-assn.org/cgi/content/abstract/archneurol.2011.2499v1