ALS and PLS; slow progression

ALS phenotype

Slow progression

Slow progression

ALS with fronto- temporal dementia

ALS disorder with Parkinsonism and dementia

Lower motor neuron disorder

ALS

22

22q12.1-q13.1

MtDNA

6q21.3

14q11.2

^a Loci for mendelian forms of ALS are listed followed by genes in which polymorphisms have been identified as risk factors in sporadic ALS.
Abbreviations: AD, autosomal dominant; ALS, amyotrophic lateral sclerosis; ApoE; apolipoprotein E; AR, autosomal recessive; DCTN1, dynactin p150 subunit; FTD, fronto-temporal dementia; HFE, haemochromatosis gene (involved in iron metabolism); MAPT, microtubule-associated protein Tau; MND, motor neuron disease; MtDNA, mitochondrial DNA; PLS, primary lateral sclerosis; SOD1, superoxide dismutase 1; VAPB, vesicle-associated membrane protein; VEGF, vascular endothelial growth factor.

References cited in Table 2

6 Rosen, D.R. et al. (1993) Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 362, 59-62, PubMed

15 Yang, Y. et al. (2001) The gene encoding alsin, a protein with three guanine-nucleotide exchange factor domains, is mutated in a form of recessive amyotrophic lateral sclerosis. Nat Genet 29, 160-165, PubMed

18 Chen, Y.Z. et al. (2004) DNA/RNA helicase gene mutations in a form of juvenile amyotrophic lateral sclerosis (ALS4). Am J Hum Genet 74, 1128-1135, PubMed

19 Figlewicz, D.A. et al. (1994) Variants of the heavy neurofilament subunit are associated with the development of amyotrophic lateral sclerosis. Hum Mol Genet 3, 1757-1761, PubMed

20 Tomkins, J. et al. (1998) Novel insertion in the KSP region of the neurofilament heavy gene in amyotrophic lateral sclerosis (ALS). Neuroreport 9, 3967-3970, PubMed

21 Al-Chalabi, A. et al. (1999) Deletions of the heavy neurofilament subunit tail in amyotrophic lateral sclerosis. Hum Mol Genet 8, 157-164, PubMed

22 Lambrechts, D. et al. (2003) VEGF is a modifier of amyotrophic lateral sclerosis in mice and humans and protects motoneurons against ischemic death. Nat Genet 34, 383-394, PubMed

23 Dhaliwal, G.K. and Grewal, R.P. (2000) Mitochondrial DNA deletion mutation levels are elevated in ALS brains. Neuroreport 11, 2507-2509, PubMed

24 Vielhaber, S. et al. (2000) Mitochondrial DNA abnormalities in skeletal muscle of patients with sporadic amyotrophic lateral sclerosis. Brain 123 ( Pt 7), 1339-1348, PubMed

25 Goodall, E.F. et al. (2005) Association of the H63D polymorphism in the hemochromatosis gene with sporadic ALS. Neurology 65, 934-937, PubMed

26 Greenway, M.J. et al. (2004) A novel candidate region for ALS on chromosome 14q11.2. Neurology 63, 1936-1938, PubMed

27 Greenway, M.J. et al. (2006) ANG mutations segregate with familial and ‘sporadic’ amyotrophic lateral sclerosis. Nat Genet 38, 411-413, PubMed

78 Puls, I. et al. (2003) Mutant dynactin in motor neuron disease. Nat Genet 33, 455-456, PubMed

145 Hand, C.K. et al. (2002) A novel locus for familial amyotrophic lateral sclerosis, on chromosome 18q. Am J Hum Genet 70, 251-256, PubMed

146 Hentati, A. et al. (1998) Linkage of a commoner form of recessive amyotrophic lateral sclerosis to chromosome 15q15-q22 markers. Neurogenetics 2, 55-60, PubMed

147 Abalkhail, H. et al. (2003) A new familial amyotrophic lateral sclerosis locus on chromosome 16q12.1-16q12.2. Am J Hum Genet 73, 383-389, PubMed

148 Sapp, P.C. et al. (2003) Identification of two novel loci for dominantly inherited familial amyotrophic lateral sclerosis. Am J Hum Genet 73, 397-403, PubMed

149 Nishimura, A.L. et al. (2004) A mutation in the vesicle-trafficking protein VAPB causes late-onset spinal muscular atrophy and amyotrophic lateral sclerosis. Am J Hum Genet 75, 822-831, PubMed

150 Hosler, B.A. et al. (2000) Linkage of familial amyotrophic lateral sclerosis with frontotemporal dementia to chromosome 9q21-q22. Jama 284, 1664-1669, PubMed

151 Hutton, M. et al. (1998) Association of missense and 5'-splice-site mutations in tau with the inherited dementia FTDP-17. Nature 393, 702-705, PubMed

152 Drory, V.E. et al. (2001) Association of APOE epsilon4 allele with survival in amyotrophic lateral sclerosis. J Neurol Sci 190, 17-20, PubMed