Amyotrophic Lateral Sclerosis: A Focus on Disease Progression

Table 1

Gene mutations described in FALS and SALS, their chromosome location, Gene mutations described in FALS and SALS, their chromosome location and their closely related molecular pathways.

Gene	Chromosome location	Deregulated pathway	Clinical features
ANG; angiogenin	14q11.2	Angiogenesis pathway	Sporadic ALS
APEX1; DNA repair enzyme endonuclease	14q11.2-q12	Oxidative stress	Sporadic ALS
C9orf72; Chromosome 9 open reading frame 72	9p21.2	RNA metabolism	Familial ALS found in sporadic; ALS, FTD
CHMP2B; chromatin modifying protein 2B	3q11.2	Endosomal trafficking	Familial ALS, FTD
CNTF; ciliary neurotrophic factor	11q12.2	Neurotrophic factor, inflammation	Sporadic ALS
DCTN1; dynactin	2q13	Deregulation of retrograde axonal transport of vesicles and organelles	Lower motor neuron disorder
FIG4; SAC domain-containing protein	6q21	Trafficking endosomal vesicles	Slow progression juvenile ALS
FUS/TLS; DNA/RNA-binding protein	16q12.1-12.2	Transcriptional regulation, RNA splicing and transport	Familial and sporadic ALS
HFE; haemochromatosis	6q21.3	Disruption of iron metabolism	Sporadic ALS
MAPT; microtubule-associated protein tau	17q21	Neurofilament structure and axonal integrity alterations	ALS disorder with Parkinsonism; and dementia
NEFL, NEFM, NEFH; neurofilaments chains	8q21; 22q12.1-q13.1	Neurofilament structure and axonal integrity alterations	Sporadic ALS
PGRN; progranulin	17q21.32	Induction of ubiquitin-positive processes, TAU-negative FTD	Sporadic ALS
PON; paraoxonase	7q21.2-q22.1	Failure in the detoxification of organophosphate and neurotoxins	Sporadic ALS
PRPH; peripherin	12q12-q13	Filament alterations in autonomic nerves and peripheral sensory neurons	Sporadic ALS
SETX; senataxin	9q34	DNA and RNA processing	Slow progression juvenile ALS
SMN; survival motor neuron gene	5q13.3	Child-onset spinal muscular atrophy linked to SMN1 mutations	Lower motor neuron disorder
SOD-1; copper/zinc superoxide-dismutase-1	21q22.1	Upregulation of protein tyrosine-nitration; Improper metal ion binding; Upregulation of proinflammatory cytokines; Formation of intracellular aggregates; Mitochondrial dysfunction; Reduced expression of glutamate transporters; Deregulation of calcium homeostasis; Downregulation of intracortical inhibitory processes; Cell death activation; Deregulation of Na+ and K+ cell gradients; Slowing of anterograde transport	Familial ALS
SPG11; spatacsin	15q15.1-21.1	Axonal transport	Slow progression juvenile ALS
TARDPB; tar DNA-binding protein	1q36.22	Neurodegeneration of neurons, oligodendroglia, and astrocytes	Familial and sporadic ALS
VAPB; vesicle-associated membrane; protein-associated protein B	20q13.33	Induction of the unfolded protein response; altered transport and secretion pathways	Familial ALS
VEGF; vascular endothelial cell growth factor	6p12	Disease severity linked to SMN2 mutations; angiogenesis, permeability blood vessels	Sporadic ALS