Variant "SOD1:p.Ala90*"
Search results: 2 records
Variant information
Gene:
SOD1 
Variant:
SOD1:p.Ala90* 
Mouse homolog:
Sod1:p.Asp90Ala 
dbSNP ID:
no data 
GWAS trait:
no data 
Modifier statisitcs
Record:
2 
Disorder:
1 
Reference:
2 
Effect type:
Expressivity(1) ,Penetrance(1)  
Modifier effect:
Altered incidence(1) ,Altered severity(1)  
Details：
  • Target disease:
    Amyotrophic Lateral Sclerosis (DOID_332)
    Effect type:
    Penetrance 
    Modifier effect:
    Altered incidence 
    Evidence:
    Assessment of genotype–phenotype associations 
    Effect:
    There is a tightly linked genetic protective factor specifically located close to the SOD1 gene in SOD1(D90A) mediated ALS.
    Reference:
    PMID19596401
    Title:
    DNA sequence analysis of the conserved region around the SOD1 gene locus in recessively inherited ALS.
    Species studied:
    Mouse
    Abstract:
    Familial amyotrophic lateral sclerosis (ALS) accounts for 10% of all ALS cases; 12-23% are associated with mutations in the Cu/Zn superoxide dismutase gene (SOD1). All ALS-linked SOD1 mutations present with a dominant pattern of inheritance apart from the aspartate to alanine mutation in exon 4 (D90A). This mutation has been observed in dominant, recessive and apparently sporadically cases. SOD1(D90A/D90A) ALS cases have a very slow disease progression (>10 years), raising the hypothesis that modifier genes linked to SOD1 ameliorate the phenotype of recessively inherited SOD1(D90A/D90A) mutations. Previous sequence analysis of a conserved haplotype region around the SOD1 gene did not reveal any functional polymorphisms within known coding or putative regulatory regions. In the current study we expanded the previous analyses by sequencing the entire SOD1 conserved haplotypic region. Although many polymorphisms were identified, none of these variants explain the slowly progressive phenotype observed in patients with recessive SOD1(D90A) mutations. This study disproves the hypothesis that there is a tightly linked genetic protective factor specifically located close to the SOD1 gene in SOD1(D90A) mediated ALS.
  • Target disease:
    Amyotrophic Lateral Sclerosis (DOID_332)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered severity 
    Evidence:
    Gene activity study 
    Effect:
    Mice carrying the mutant human SOD1 transgenes can greatly increase our ability to properly assess the impact and implications for the role of various genes in the development of ALS
    Reference:
    PMID21241159
    Title:
    Effect of genetic background on phenotype variability in transgenic mouse models of amyotrophic lateral sclerosis: a window of opportunity in the search for genetic modifiers.
    Species studied:
    Mouse
    Abstract:
    Transgenic (Tg) mouse models of FALS containing mutant human SOD1 genes (G37R, G85R, D90A, or G93A missense mutations or truncated SOD1) exhibit progressive neurodegeneration of the motor system that bears a striking resemblance to ALS, both clinically and pathologically. The most utilized and best characterized Tg mice are the G93A mutant hSOD1 (Tg(hSOD1-G93A)1GUR mice), abbreviated G93A. In this review we highlight what is known about background-dependent differences in disease phenotype in transgenic mice that carry mutated human or mouse SOD1. Expression of G93A-hSOD1Tg in congenic lines with ALR, NOD.Rag1KO, SJL or C3H backgrounds show a more severe phenotype than in the mixed (B6xSJL) hSOD1Tg mice, whereas a milder phenotype is observed in B6, B10, BALB/c and DBA inbred lines. We hypothesize that the background differences are due to disease-modifying genes. Identification of modifier genes can highlight intracellular pathways already suspected to be involved in motor neuron degeneration; it may also point to new pathways and processes that have not yet been considered. Most importantly, identified modifier genes provide new targets for the development of therapies.