11 September 2023
Genetic mutation linked to juvenile ALS
Published online 31 August 2011
Amyotrophic lateral sclerosis (ALS), otherwise known as Lou Gehrig's disease, is a neurodegenerative disease that affects motor neurons in the upper and lower limbs. This rare condition afflicts between 1 and 3 per 100,000 of the population and leads to paralysis and eventual death, most likely from respiratory failure. Around 10% of cases have a family history. While the onset of the disease usually occurs after 46 years of age, a milder juvenile form of ALS starts before 25 years of age.
Researchers from the King Faisal Specialist Hospital and Research Center, Riyadh, performed gene mapping of four juvenile ALS patients from a consanguineous family from the eastern region of Saudi Arabia, and publish their results in Annals of Neurology.
They discovered a mutation in the SIGMAR1 gene causes juvenile ALS. The gene encodes the Sigma-1 receptor (Sig-1R),.which studs the cell membranes of several tissues including the central nervous system. The mutation leads to the substitution of glutamine for glutamic acid at a specific position in the receptor. The mutated cells were more prone to apoptosis during stress than cells carrying the wild-type Sig-1R.
Further research is needed to determine the exact role of Sig-1R in the pathogenesis of ALS, and to identify any potential therapeutic targets. The protein is thought to have neuroprotective properties and it is involved in ion channel modulation through interaction with K+ channels. It also has a chaperone role at the endoplasmic reticulum. The researchers suggest the mutation may lead a loss of function of Sig-1R but further experiments are required for verification.
- Al-Saif, A. et al. A Mutation in Sigma-1 Receptor Causes Juvenile Amyotrophic Lateral Sclerosis. Annals of Neurology (12 August 2011) doi:10.1002/ana.22534