Table 4

Genetics of MND (ALS—amyotrophic lateral sclerosis) (modified from Kato et al, 2003, with permission)

Type of familial ALS and pattern of inheritanceChromosomal linkageGene/protein
1. Autosomal dominant familial ALS21q22.1–22.2
 (ALS1) Over 100 mutations in SOD1 gene, mostly missense mutations, some nonsense mutations leading to truncated proteinCu/Zn superoxide dismutase 1 (SOD1)
2. Autosomal dominant juvenile ALS9q34 (ALS4)
 Slowly progressive childhood or adolescent onset UMN and LMN syndromeUnknown
3. Autosomal dominant familial ALS with fronto-temporal dementia9q21–q22 (ALS-FTD)
 Several families with ALS, ALS plus dementia, or dementia alone. Dementia is of frontotemporal typeUnknown
4. X linked dominant familial ALSXcentromere (ALSX)Unknown
5. Autosomal recessive juvenile familial ALS2q33–2q35 (ALS2)
 Several families slowly progressive spastic quadriparesis. Some LMN signs in one family. Pathology unknownALS2/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 ALS15q15–15q22 (ALS5)Unknown
7. Autosomal dominant familial ALS18q21 (ALS6)Unknown
8. Autosomal dominant familial ALS16q12; variable penetrance.Unknown
4 families known. Typical ALS, and ALS with dementia
9. Autosomal dominant familial ALSUnknown (ALS3) (,80% of families)Unknown
10. Autosomal Recessive Fazio-Londe disease (pontobulbar palsy of childhood without deafness)UnknownUnknown
11. Autosomal recessive Brown-Vialetto-Van Laere syndrome (pontobulbar palsy of childhood with sensorineural deafness)UnknownUnknown
Possibly same as Madras phenotype
12. Autosomal dominant familial amyotrophy with frontotemporal dementia, and parkinsonism17q21–17q22
 Many phenotypes, mainly FTD, parkinsonism and a few associated with MNDTau gene/protein