Table 1 UBQLN2 mutations in ALS patients
From: Key role of UBQLN2 in pathogenesis of amyotrophic lateral sclerosis and frontotemporal dementia
Forms of ALS | Age at onset (years) | Mutations | Domain | Clinical features | Neuropathology | Ref. |
|---|---|---|---|---|---|---|
Familial | 16 to 71 | P497H P497S P506T P509S P525S | PXX | Earlier onset in male (33.9 ± 14.0) than female (47.3 ± 10.8), ALS, ALS/FTD and pure FTD | TDP-43/UBQLN2 NCI in spinal cord and hippocampus | [12] |
Familial | 30 to 76 | T487I | PXX | Earlier onset in male (39.5 ± 10.4) than female (51.2 ± 14.3), pure ALS, bulbar and spinal onset | FUS/UBQLN2/TDP-43/ubiquitin NCI in the spinal cord | [64] |
Sporadic | 51 to 73 | Q425R A282V A283T | Outside domains | ALS and pure FTD, spinal onset | n/a | [59] |
Familial | 30 to 57 | P506S P533L M446R V538 L N439I | PXX | ALS and ALS/FTD, spinal and bulbar onset | n/a | [18] |
Sporadic | 46 to 59 | S155 N P189T | S155 N: outside P189T: STI-1 | Pure ALS, bulbar and spinal onset | n/a | [11] |
Familial | 4 to 63 | P497L | PXX | Phenotype diversity: Choreoathetoid movements, dysarthria, spastic paralysis, ALS, FTD | UBQLN2/TDP-43 NCI in brain stem and hippocampus, striatal atrophy, cerebral atrophy | [16] |
Familial and sporadica | 27–62 | P494L P500S P506A A488T | PXX A488T: outside | ALS and spastic paraplegia | n/a | [60] |
Sporadic | 62 | M392 V | STI1 | Pure ALS | n/a | [26] |
Sporadic | 14–16 | M392I | STI1 | Madras-type MND | n/a | [46] |
Familial | 52 | p.Gly502_Ile504del | PXX | Bulbar ALS | n/a | [41] |
Sporadic | 30–77 | S346C S400G P440L | Outside STI1 | Pure FTD (S346C) and pure ALS | n/a | [13] |