Mutational analysis of the Cu/Zn superoxide dismutase gene in 23 familial and 69 sporadic cases of amyotrophic lateral sclerosis in Belgium

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative diso rder caused by degeneration of motor neurons of the spinal cord and brain. The majority of ALS cases are sporadic (SALS), However, in 10-15% of ALS ca ses the disease is inherited as an autosomal dominant trait (familial ALS o r FALS), We used a non-radioactive SSCP method, in combination with solid p hase sequencing, to screen the entire SOD1 (Cu/Zn superoxide dismutase) cod ing region and flanking intronic sequences for mutations, Twenty-three pati ents from 11 ALS families and 69 SALS patients of Belgian origin were studi ed. Three different mutations were identified (L38V, D90A and G93C) in seve n families, Importantly, the D90A was only found in the heterozygous state. In addition two single base pair variants (IVS1 + 19G > A and AAC139 AAT) were identified in two SALS patients, These results suggest that the SOD1 a nalysis is useful in FALS but less so in SALS cases. The SSCP analysis has proved fast and reliable for this purpose.