An Iranian familial amyotrophic lateral sclerosis pedigree with p.Val۴۸Phe causing mutation in SOD۱: a genetic and clinical report

Objective(s): Amyotrophic lateral sclerosis (ALS), a fatal progressive neurodegenerative disorder, is the most common motor neuron disease in European populations. Approximately ۱۰% of ALS cases are familial (FALS) and the other patients are considered as sporadic ALS (SALS). Among many ALS causing genes that have been identified, mutations in SOD۱ and C۹orf۷۲ are the most common genetic causes of the disease. In Iranian patients, it has been shown that SOD۱, as compared to C۹orf۷۲, plays a much more prominent role.  To date, more than ۱۷۰ mutations have been reported in SOD۱. Genotype/phenotype correlation with respect to either different causative genes or different mutations of a specific gene has not been well established.  Materials and Methods: Five exons of SOD۱ and flanking intronic sequences of an Iranian FALS proband were screened for mutations by direct sequencing. Also, the clinical features of the proband were described. Results: Heterozygous p.Val۴۸Phe causing mutation was identified in SOD۱. Age at onset was ۲۹ years and site of the first presentation was the lower extremity in the proband. Conclusion: The p.Val۴۸Phe causing mutation appears to cause early onset of ALS.

Keywords:

ALS , Aamyotrophic lateral sclerosis , SOD۱ , Superoxide dismutase ۱ gene , p.Val۴۸Phe