Some examples of genotype/phenotype correlations in MND associated with specific SOD1 gene mutations
| Mutation | Inheritance | Penetrance in affected families | Distribution, phenotype | Survival from onset of symptoms |
|---|---|---|---|---|
| Alanine to valine, exon 1, codon 4 (A4V) Aspartate to alanine, exon 4, codon 90 (D90A) | Autosomal dominant | Complete | North America. Rapidly progressive mainly LMN syndrome, limb or bulbar onset | <2 years |
| Autosomal recessive (homozygous): “Scandinavian recessive D90A MND/ALS” | Complete | Scandinavia; Russia, France, Germany, North America. Slowly progressive, presenting as spastic paraparesis, evolving into limb and bulbar MND. Bladder and sensory symptoms common | 10–20 years | |
| Aspartate to alanine, exon 4, codon 90 (D90A) | Autosomal dominant (heterozygous) | Variable | Belgium, UK, USA, Russia. Variable phenotype | Variable; short or long survival |
| Glutamate to lysine, exon 4, codon 100 (E100K) | Autosomal dominant | Variable | Afro-American, German families; variable phenotype | >10 years |
| Isoleucine to threonine, exon 4, codon 113 (I113T) | Autosomal dominant | Very variable; apparently sporadic cases with I113T mutation not uncommon | North America, Scotland. Variable phenotype | Variable; short or long (>10 years) |