E-Pearl of the Week: Genetics of Sporadic Amyotrophic Lateral Sclerosis

August 28, 2012


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August 28, 2012

Genetics of Sporadic Amyotrophic Lateral Sclerosis

Several genetic mutations can be associated with sporadic ALS and some of them are more common than previously thought. While superoxide dismutase 1 (SOD1) mutation was thought to be the most common genetic mutation known to be associated with sporadic ALS, recently the chromosome 9 open reading frame 72 (C9ORF72) mutations have been found to be more common. The frequency of SOD1 mutation is estimated to be approximately 2% in patients with sporadic ALS, while the mutation of C9ORF72 gene varies between 2.5%–21% of patients with sporadic ALS. Other genetic mutations associated with ALS include angiogenin loss of function, TAR DNA binding protein, fused in sarcoma, and optineurin, among others.


  1. Renton AE, Majounie E, Waite A et al. A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21–linked ALS–FTD. Neuron 2011;72: 257–268.
  2. Lattante S, Conte A, Zollino M et al. Contribution of major amyotrophic lateral sclerosis genes to the etiology of sporadic disease. Neurology 2012;79: 66–72.
  3. van Rheenen W, van Blitterswijk M, Huisman M. et al. Hexanucleotide repeat expansions in C9ORF72 in the spectrum of motor neuron diseases Neurology 2012; 79: 878–882.

Submitted by Chafic Karam, MD

Disclosure: Dr. Karam serves on the editorial team for the Neurology Resident and Fellow Section.

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