Analysis of a genetic defect in the TATA box of the SOD1 gene in a patient with familial amyotrophic lateral sclerosis.

We report a patient with autosomal-dominant amyotrophic lateral sclerosis (ALS) and a sequence variation in the SOD1 promoter region, located in the conserved TATA box motif (TATAAA -> TGTAAA). Functional promoter studies of this variant in an in vitro system showed moderate reduction in transcriptional activity of SOD1. This variant was present in only two of 301 individuals with sporadic amyotrophic lateral sclerosis, was not detected in 396 matched controls, and was recently reported in dbSNP (rs7277748). Our data suggest that this TATA box defect is not a disease-causing mutation or susceptibility factor for ALS but rather a rare polymorphism with a potential effect on SOD1 gene expression.