Genetics of amyotrophic lateral sclerosis: more than twenty years of studies

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Amyotrophic lateral sclerosis, also known as motor neuron disease or Lou Gehrig’s disease, is an adult-onset neurodegenerative disease that targets motor neurons in the spinal cord, cortex and brain stem. Selective degeneration of corticospinal (upper) and spinal (lower) motor neurons manifests as a linear decline in muscular function, eventually resulting in paralysis, speech and swallowing deficits and death, usually from impaired respiratory function, over a time course of approximately 3-5 years.

1. Chio A, Logroscino G, Traynor BJ et al. Global epidemiology of amyotrophic lateral sclerosis: a systematic review of the published literature. Neuroepidemiology 2013; 41: 118-30.

2. Rosen DR, Siddique T, Patterson D et al. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 1993; 362: 59-62.

3. Vance C, Rogelj B, Hortobágyi T et al. Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science 2009 February 27; 323(5918): 1208-1211.

4. Sreedharan J, Blair IP, Tripathi VB et al. TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science 2008; 319: 1668-1672.

5. Polymenidou M, Lagier-Tourenne C, Hutt KR et al. Misregulated RNA processing in amyotrophic lateral sclerosis. Brain Res 2012; 1462: 3-15.

6. Maruyama H, Morino H, Ito H et al. Mutations of optineurin in amyotrophic lateral sclerosis. Nature. 2010; 465:223- 226.

7. Chio A, Calvo A, Mazzini L et al. Extensive genetics of ALS: a population- based study in Italy. Neurology. 2012; 79:1983-1989.

8. Johnson JO, Mandrioli J, Benatar R et al. Exome sequencing reveals VCP mutations as a cause of familial ALS. Neuron. 2010; 68:857-864.

9. DeJesus-Hernandez M, Mackenzie I, Bradley F. Boeve et al. Expanded GGGGCC hexanucleotide repeat in non-coding region of C9ORF72 causes chromosome 9p-linked frontotemporal dementia and amyotrophic lateral sclerosis. Neuron. 2011 October 20; 72(2): 245-256. doi:

10. 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 Oct 20;72(2):257-68. doi:

11. Brown RH, Al-Chalabi A. Amyotrophic lateral sclerosis. N Engl J Med. 2017; 13;377(2):162-172.

12. Ji AL, Zhang X, Chen WW, Huang WJ et al. Genetics insight into the amyotrophic lateral sclerosis/frontotemporal dementia spectrum. J Med Genet. 2017; 54(3):145-154

13. Millecamps S, Boillee S, Le Ber I et al. Phenotype difference between ALS patients with expanded repeats in C9ORF72 and patients with mutations in other ALS-related genes. J Med Genet. 2012 Apr;49(4):258-63.

14. Lill CM, Abel O, Bertram L et al. Keeping up with genetic discoveries in amyotrophic lateral sclerosis: The ALSoD and ALSGene databases. Amyotroph Lateral Scler 2011; 12: 238-249.

15. Smith BN, Ticozzi N, Fallini C et al. Exome-wide rare variant analysis identifies TUBA4A mutations associated with familial ALS. Neuron. 2014 Oct 22;84(2):324-31.

16. Cirulli ET, Lasseigne BN, Petrovski S et al. Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways. Science. 2015 Mar 27;347(6229):1436-41.

17 - Fogh I, Ratti A, Gellera C et al. A genome-wide association meta- analysis identifies a novel locus at 17q11.2 associated with sporadic amyotrophic lateral sclerosis. Hum Mol Genet. 2014 Apr 15;23(8):2220-31.

18. Rheenen W, Shatunov A, Dekker AM et al. Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis. Nat Genet. 2016 Sep;48(9):1043-8.

19. Elden AC, Kim HJ, Hart MP et al. Ataxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALS. Nature. 2010 Aug 26;466(7310):1069-75.

20. Wang MD, Gomes J, Cashman NR et al. Intermediate CAG repeat expansion in the ATXN2 gene is a unique genetic risk factor for ALS − A systematic review and meta-analysis of observational studies. PLoS One. 2014; 9(8): e105534.

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