From animal models to human disease: a genetic approach for personalized medicine in ALS

Table 1 Clinical characteristics of human SOD1 mutations reproduced in animal models

Mutation	Mean age at onset (y ± SD)	Site at onset	Survival (yr ± SD)	Clinical manifestations				References
Mutation	Mean age at onset (y ± SD)	Site at onset	Survival (yr ± SD)	UMN	LMN	Cognitive symptoms	Neuropathological findings	References
A4V	47.8 ± 13.3	Limbs	1.4 ± 0,9	Mild	Y, Pred	N	LBHI, NCI	[53, 232, 233]
G37R	40.0 ± 9.9	Limbs	18.7 ± 11.4	Y	Y	N	LBHI	[22, 43, 54]
H46R	49.6 ± 10.9	Legs	17.3 ± 10.7	Y	Y, Pred	N	LBHI	[55, 234]
H48Q	54	nd	8 months	nd	Y, Pred	nd	LBHI,SLI	[56, 235]
L84V	53.8 ± 15.3	Arms	1.6 ± 0.5	Y	Y, Pred	N	nd	[236, 237]
D83G	55	Legs	6	Y	Y, Pred	N	nd	[46]
G85R	nd	nd	nd	nd	nd	nd	nd	[43]
D90A	44	Legs	13	Y	Y	nd	nd	[45, 52]
G93A	47.4 ± 12.4	Limbs	10.0 ± 6.2	nd	nd	N	nd	[22, 43]
I113T	58.9 ± 12.6	Limbs	3.5 ± 2.8	nd	Y, pred	Y	NFT, ICAI, HC, NFCI	[22, 43, 50, 57, 238–240]
L126Z	58	nd	4	nd	Y	nd	LBHI	[58, 241]
G127X	50	Limbs	2.8	Y	Y	nd	nd	[242]

nd not described, UMN upper motor neuron signs, LMN lower motor neuron signs, N no, Y yes, Pred predominant, LBHI lewy-body-like hyaline inclusion, NCI neuronal cytoplasmic inclusion, SLI skein-like inclusion, HC hyaline conglomerate, ICAI intracytoplasmic argyrophilic inclusion (neurofilament accumulation), NFCI neurofilamentous conglomerate inclusion

ISSN: 2051-5960