A NOVEL SOD1 MUTATION IN AN AUSTRIAN FAMILY WITH AMYOTROPHIC-LATERAL-SCLEROSIS

We report on an Austrian pedigree with autosomal dominant amyotrophic lateral sclerosis (ALS), diagnosed in six patients from two generation s. The only surviving clinically affected family member was examined i n our ALS clinic. Historical information on other affected individuals was obtained from knowledgeable family members. The mean +/- S.D. age of onset of the disease was 54 +/- 6.9 years, with a range of 43-66 y ears. The duration of;he index patient's disease until death was 8 mon ths. Using single strand conformational polymorphism (SSCP) analysis, we studied the index patient's exons 1, 2 and 4 of the Cu/Zn superoxid e dismutase gene (SODI) on chromosome 21. A variant banding pattern wa s observed for exon 1. Sequencing studies showed a previously undescri bed T to A missense mutation at position 8 in exon 1 of the SOD1 gene. This mutation results in the elimination of an Eco57I restriction sit e. Whereas the index patient was heterozygous for this restriction sit e, 50 unrelated healthy controls and an unaffected brother were not. T he mutation lies in a region involved in dimer contact in the three-di mensional structure of the SOD1 protein. This region comprises other k nown sites for ALS-causing mutations. (C) 1997 Elsevier Science B.V.