|| common in clinvar
|| Carrier of a Canavan disease mutation
|| Canavan disease (predicted)
rs28940279, also known as E285A or Glu285Ala, is a SNP in the ASPA gene.
rs28940279 is one of several known causal SNPs of Canavan disease. Canavan disease is a degenerative disease of the nervous system. It is a childhood onset disease which begins in early infancy. It is characterized by disordered muscular behavior (e.g., hypotonia, hyperextension) and neurological symptoms, such as blindness, developmental and cognitive delays. The neurological findings appear to be due to demyelination and leukodystrophy. Histology indicates the presence of spongy degeneration; cytology confirms astrocytic swelling of normal neurons and abnormality of astrocyte mitochondria.
[PMID 3354621] Ultimately, sufferers become extremely ill and die on average at 18 months of age.
rs28940279 is a SNP in the aspartoacylase ASPA gene.
[PMID 8252036] The A-C transversion results in a substitution of alanine, a hydrophobic small-chain amino acid, for a glutamate (which is both large and charged). This substitution, E285A, is at a residue predicted to be part of the catalytic domain of aspartocyclase. This missense mutation is predicted to have drastic effects on the catalytic domain because of the vast difference between the amino acids.
In particular, this substitution is common in Ashkenazi Jews, with carrier frequency approximately 1 in 60 individuals.
[PMID 8037206] This suggests that some degree of founder effect is responsible for its prevalence within the Ashkenazi Jewish population. In particular, one study suspects that the mutation originated in the Vilna area, in Poland or Lithuania depending on the political timeperiod of origin.
[PMID 14239091] This suggests that it is a newer variant than others found in the more broad European population.