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Table 2 Genetic contribution to the risk and progression of ALS using NGS

From: The role of gene variants in the pathogenesis of neurodegenerative disorders as revealed by next generation sequencing studies: a review

Study Methods Risk of ALS ALS course
Couthouis et al., 2014 [41] Targeted sequencing of 169 ALS genes in 242 sporadic ALS patients 134 novel variants were found in ALS patients versus 61 in controls. 99 rare variants were found in ALS patients versus 41 in controls. Deleterious novel and rare variants were enriched in cases vs. controls (p = 0.019). APOE ε2 allele was associated with limb onset and ε4 allele was associated with earlier age of onset in limb onset ALS.
Cady et al., 2015 [43] Targeted pooled-sample sequencing of 17 ALS genes in 391 sporadic and familial ALS patients 64.3% of familial and 27.8% of sporadic ALS patients had novel or rare variants. 3.8% of patients had variants in more than 1 ALS gene. Patients with variants in more than 1 ALS gene had earlier disease onset by 10 years.
Pang et al., 2017 [42] WGS of 8 familial ALS patients and WES of 46 sporadic ALS patients Variants in 40 ALS genes were examined 67% had one variant; 22% had two or more. Presence of rare variants was significantly associated with risk of ALS (p = 0.03). ALS patients had significantly higher rare variant burden than controls (p = 0.004). FALS patients with additional rare variants had shorter survival compared with FALS patients with only one mutation. In sporadic and familial ALS, each additional rare variant increased the risk of ventilatory failure or death by 60%. Patients with two or more variants had significantly lower probability of survival than patients with zero or one variant (p = 0.001).