Paraoxonase gene mutations in amyotrophic lateral sclerosis

Abstract

Three clustered, homologous paraoxonase genes (PON1, PON2, and PON3) have roles in preventing lipid oxidation and detoxifying organophosphates. Recent reports describe a genetic association between the PON genes and sporadic amyotrophic lateral sclerosis (ALS). We now report that in genomic DNA from individuals with familial and sporadic ALS, we have identified at least 7 PON gene mutations that are predicted to alter PON function.

Figures

Figure 1. Evolutionary Conservation of PON Mutations in Familial and Sporadic ALS

This illustrates the evolutionary conservation of the amino acids implicated by the 8 identified mutations. For each, the mutated amino acid (or nucleotide for the splicing mutation) is shown in red. Chromatograms displaying the mutation are shown below. The position indicates the base pair position within the cDNA. All mutations were heterozygous except for the homozygous C42Y PON2 mutation. Each mutation was confirmed by bi-directional sequencing and 5’ nuclease assay genotyping.