Table 1 The genotype and phenotype associated with familial ALS-related genes
From: Genotype-phenotype relationship in hereditary amyotrophic lateral sclerosis
Type | Gene | Mode of inheritance | Country | Age at onset (range) | Mean age at onset (years) | Initial symptoms | UMN | Cognitive impairment | Other features |
|---|---|---|---|---|---|---|---|---|---|
ALS1 | SOD1 | AD, AR, de novo | Japan, Italy, Spain, Korea, UK, USA, Turkey, Sweden, Iran, Porland, Bulgaria, China, France, Germany, Denmark, Pakistan, Canada, and so on | 6–94 | 48 | LL > UL > bulbar | Positive (LMN dominant) | Very rare | Progressive muscular atrophy, progressive bulbar palsy, facial onset sensory motor neuronopathy (FOSMN) syndrome, vocal cord paralysis, cerebellar ataxia, sensory disturbance (vibration), autonomic dysfunction (incontinence, neurogenic bladder), lower back pain |
ALS2 | Alsin | AR | Tunisia, Saudi Arabia, Kuwait, Italy, Algeria, Hungary, Germany, The Netherlands, Pakistan, Bangladesh, Turkey, Japan, Portugal, France, Cyprus, China | 1–11 | 2 | LL, UL | Positive | None | Juvenile ALS, juvenile primary lateral sclerosis, infantile-onset ascending hereditary spastic paraplegia, generalized dystonia, cerebellar ataxia |
ALS3 | unknown | AD | Â | Â | Â | Â | Â | Â | Â |
ALS4 | SETX | AD | USA, Austria, Belgium, Italy, Afghanistan, China | 1–73 | 19 | LL > UL | Positive | None | Cerebellar ataxia, oculomotor apraxia (type 2), motor neuropathy, thin cervical spinal cord |
ALS5 | SPG11 | AR | Italy, Turkey, Japan, Canada, Brazil | 7–23 | 16 | Bulbar, LL, UL | Positive | Rare (mental retardation) | Juvenile ALS, hereditary spastic paraparesis, autonomic dysfunction (incontinence) |
ALS6 | FUS | AD, AR, de novo | Belgium, Italy, Korea, UK, Japan, Turkey, Canada, France, USA, Germany | 13–80 | 45 | UL, bulbar > LL | Positive (LMN dominant) | Rare (mental retardation) | Progressive muscular atrophy, Parkinsonism, essential tremor, schizofrenia, learning disabilities |
ALS7 | unknown | AD | Â | Â | Â | Â | Â | Â | Â |
ALS8 | VAPB | AD | Brazil, UK, France (Japan), The Netherlands | 18–73 | 44 | UL, LL | Negative | None | Progressive muscular atrophy, progressive bulbar palsy, motor neuropathy, postural tremor, autonomic dysfunction (chronic intestinal constipation, sexual dysfunction) |
ALS9 | ANG | AD | The Neitherland, Ireland, Scotland, UK, USA, Sweden, Italy, France, Germany, China, | 21–86 | 55 | UL, LL, bulbar | Positive | FTD | Parkinsonism, progressive bulbar palsy |
ALS10 | TDP-43 | AD, AR | Italy, France, UK, China, Germany, Turkey, USA, Belgium, Japan, Porland, Afghaistan, Canada | 20–77 | 54 | UL, LL, bulbar | Positive | FTD (rare) | Parkinsonism, chorea, progressive supranuclear palsy |
ALS11 | FIG4 | AD | USA | 29–77 | 55 | Bulbar > UL, LL | Positive | None | Hereditary spastic paraparesis, primary lateral sclerosis, personality change |
ALS12 | OPTN | AD, AR | Japan, Italy, Turkey, The Netherlands, Denmark | 24–83 | 51 | Bulbar, UL, LL | Positive | FTD, AGD | Primary open angle glaucoma, parkinsonism, finger deformity, personality change, depression |
ALS13 | ATXN2 | AD | USA, Belgium, the Netherlands, Canada, France, China, Germany, Switzerland, Italy, Turkey, Cuba | 21–87 | 60 | UL, LL | Positive | None | Cerebellar ataxia, corticobasal syndrome, Parkinsonism |
ALS14 | VCP | AD | Italy, USA, The Netherlands, Japan | 36–68 | 48 | LL > UL > bulbar | Positive | FTD | Paget’s Disease, inclusion body myopathy |
ALS15 | UBQLN2 | SD | USA, Australia, Canada, Italy, Turkey, Belgium, Germany, Bulgaria | M: 14-72, F: 16-77 | 44 | UL, LL, bulbar | Positive | FTD | Primary lateral sclerosis, progressive bulbar palsy, relentlessly progressive choreoathetoid movements, spastic paralysis |
ALS16 | SIGMAR1 | AD | Saudi Arabia | 1-68 | 1 | LL > UL | Positive | FTD (rare) | Juvenile ALS |
ALS17 | CHMP2B | AD | Denmark, the Netherlands | 26-73 | 69 | Bulbar, UL, LL, respiratory | Positive (LMN dominant) | FTD | Progressive muscular atrophy, parkinsonism |
ALS18 | PFN1 | AD | Sephardic Jewish, Italy, USA, China, Belgium | 33-63 | 53 | Limb | N/A | N/A | Â |
ALS19 | ERBB4 | AD | Japan, Canada | 45-70 | 61 | UL, bulbar, respiration | Positive | None | Â |
ALS20 | HNRNPA1 | AD | N/A | N/A | N/A | N/A | N/A | FTD | Paget’s Disease, inclusion body myopathy |
ALS21 | MATR3 | AD | USA,UK, Italy, Taiwan | 36-64 | 52 | LL > UL, bulbar | Positive | FTD | Distal myopathy (inclusion body myopathy) |
ALS-FTD1 | C9ORF72 | AD | Finland, Sardinia, Ireland, UK, Italy, USA,Canada, Germany, the Netherlands, Turkey, Israel, Australia, Japan | 27–80 | 57 | UL, LL, bulbar | Positive | FTD | Parkinsonism, cerebellar ataxia, psychosis, |
ALS-FTD2 | CHCHD10 | AD | France, USA, Germany, Spain, Italy, Finland | 35-73 | 56 | Bulbar, UL, LL | Positive (LMN dominant) | FTD | Cerebellar ataxia, mitochondrial myopathy, deafness, neurogenic bladder, facial paresis, Parkinsonism |
| Â | TBK1 | AD, de novo | Sweden, Denmark, Germany, France, Portugal | 35-80 | 60 | Bulbar, UL, LL, respiratory | Positive | FTD (50Â %) | Â |