Table 1 |.
Human disease | Findings | Comment | Refs |
---|---|---|---|
Alzheimer disease | NMNAT2 protein and mRNA are reduced in brains of individuals with Alzheimer disease | This finding suggests that reduced NMNAT2 is associated with, and may be a risk factor for, the development of Alzheimer disease | 95 |
Erythromelalgia and peripheral neuropathy | A homozygous NMNAT2 partial loss-of-function mutation in two individuals with erythromelalgia and peripheral neuropathy | Loss-of-function mutation in NMNAT2 results in development of peripheral neuropathy | 89 |
Fetal akinesia deformation syndrome | Compound heterozygous NMNAT2 severe loss-of-function mutations in two fetuses with fetal akinesia deformation syndrome | Severe loss-of-function mutation in NMNAT2 results in stillbirth, mimicking observations in NMNAT2 null mice | 90 |
ALS | GWAS show association of the SARM1 locus with ALS | A pathogenic role of SARM1 in ALS must involve gain-of-function variants that increase the risk of axonal degeneration | 101,102 |
ALS | An ALS-causing mutation in TARDBP reduces levels of stathmin 2 in iPSC-derived motor neurons; a similar decrease is common in sporadic ALS | Low levels of stathmin 2 increase the likelihood of Wallerian degeneration and could therefore be an important modifier or risk factor for ALS | 96,97 |
ALS, amyotrophic lateral sclerosis; GWAS, genome-wide association studies; iPSC, induced pluripotent stem cell; NMNAT2, nicotinamide mononucleotide adenylyltransferase 2; SARM1, sterile-α and Toll/interleukin 1 receptor (TIR) motif containing protein 1; TDP43, transactive response DNA binding protein 43 kDa.