Genetic analysis and SOD1 mutation screening in Iranian amyotrophic lateral sclerosis patients

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease, and the most common in European populations. Results of genetic analysis and mutation screening of SOD1 in a cohort of 60 Iranian ALS patients are here reported. Initially, linkage analysis in 4 families identified a disease-linked locus that included the known ALS gene, SOD1. Screening of SOD1 identified homozygous p.Asp90Ala causing mutations in all the linked families. Haplotype analysis suggests that the p.Asp90Ala alleles in the Iranian patients might share a common founder with the renowned Scandinavian recessive p.Asp90Ala allele. Subsequent screening in all the patients resulted in identification of 3 other mutations in SOD1, including p.Leu84Phe in the homozygous state. Phenotypic features of the mutation-bearing patients are presented. SOD1 mutations were found in 11.7% of the cohort, 38.5% of the familial ALS probands, and 4.25% of the sporadic ALS cases. SOD1 mutations contribute significantly to ALS among Iranians.