Genetics of MND (ALS—amyotrophic lateral sclerosis) (modified from Kato et al, 2003, with permission)
| Type of familial ALS and pattern of inheritance | Chromosomal linkage | Gene/protein |
|---|---|---|
| 1. Autosomal dominant familial ALS | 21q22.1–22.2 (ALS1) Over 100 mutations in SOD1 gene, mostly missense mutations, some nonsense mutations leading to truncated protein | Cu/Zn superoxide dismutase 1 (SOD1) |
| 2. Autosomal dominant juvenile ALS | 9q34 (ALS4) Slowly progressive childhood or adolescent onset UMN and LMN syndrome | Unknown |
| 3. Autosomal dominant familial ALS with fronto-temporal dementia | 9q21–q22 (ALS-FTD) Several families with ALS, ALS plus dementia, or dementia alone. Dementia is of frontotemporal type | Unknown |
| 4. X linked dominant familial ALS | Xcentromere (ALSX) | Unknown |
| 5. Autosomal recessive juvenile familial ALS | 2q33–2q35 (ALS2) Several families slowly progressive spastic quadriparesis. Some LMN signs in one family. Pathology unknown | ALS2/Alsin Alsin is a guanine exchange factor (GEF) and is implicated in signal transduction and a variety of other cellular processes |
| 6. Autosomal recessive juvenile familial ALS | 15q15–15q22 (ALS5) | Unknown |
| 7. Autosomal dominant familial ALS | 18q21 (ALS6) | Unknown |
| 8. Autosomal dominant familial ALS | 16q12; variable penetrance. | Unknown |
| 4 families known. Typical ALS, and ALS with dementia | ||
| 9. Autosomal dominant familial ALS | Unknown (ALS3) (,80% of families) | Unknown |
| 10. Autosomal Recessive Fazio-Londe disease (pontobulbar palsy of childhood without deafness) | Unknown | Unknown |
| 11. Autosomal recessive Brown-Vialetto-Van Laere syndrome (pontobulbar palsy of childhood with sensorineural deafness) | Unknown | Unknown |
| Possibly same as Madras phenotype | ||
| MND | ||
| 12. Autosomal dominant familial amyotrophy with frontotemporal dementia, and parkinsonism | 17q21–17q22 Many phenotypes, mainly FTD, parkinsonism and a few associated with MND | Tau gene/protein |