Four families with slowly progressive ALS due to p.Val120Leu SOD1 variant in Northeast Brazil

<i>Objective</i>: SOD1 mutations are the second most prevalent variants in amyotrophic lateral sclerosis (ALS). Epidemiological data about SOD1 mutations are scarce in Brazil. Here, we report the clinical and genetic findings of four Brazilian families with p.Val120Leu SOD1 variant. <i>Methods</i>: This study is part of an epidemiological study of the prevalence of ALS conducted in the State of Ceará, Brazil. We reviewed the medical records of families with p.Val120Leu (c.358G > C, exon 5) SOD1 variant seen at the Walter Cantídio University Hospital, Federal University of Ceará, Brazil. <i>Results</i>: We identified 15 patients from 4 families with p.Val120Leu SOD1 variant among 251 ALS patients. Of these, six were personally examined and had ALS confirmed and five had confirmatory genetic testing (four homozygous and one heterozygous). C9orf72 testing was normal in the heterozygous patient. In two families, three older heterozygous patients (genetically tested) had no signs or symptoms of ALS. The mean age of symptom onset was 46.7 ± 13.4 years. Features of ALS in the four families were very similar, with prolonged disease duration and upper and lower motor neuron involvement, fulfilling the Revised El Escorial, Awaji, and Gold Coast diagnostic criteria. All examined living patients had limb onset and a few bulbar symptoms. <i>Conclusion</i>: p.Val120Leu SOD1 variant leads to slowly progressive ALS with incomplete penetrance. Our findings are similar to a previous report of ALS due to p.Asp90Ala SOD1 variant.