Clinical characteristics of familial amyotrophic lateral sclerosis with a Phe20Cys mutation in the SOD1 gene in a Korean family

Abstract

Familial ALS (FALS) is mostly inherited as an age-dependent autosomal dominant trait. Since the discovery of mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1), testing for SOD1 gene mutations has become a routine part of the investigation into ALS patients with a family history. This study reports the results of mutation evaluation and clinical features examination in a Korean family with ALS. The clinical symptoms, signs and neurological findings of a four-generation pedigree with 34 members were collected. Five exons of the Cu/Zn SOD gene were analyzed by polymerase chain reaction. The clinical signs and symptoms of ALS patients began in the lower extremities and spread to the upper extremities and bulbar muscles. The mode of transmission was determined to be autosomal dominant, and low penetrance was seen in females. The age at onset varied from 37 to 77 years. ALSFRS-R testing showed variability in the clinical progression of the disease. A point mutation in exon 1 of the SOD1 gene, resulting in an amino acid change from phenylalanine 20 to cysteine (F20C), was identified. This is the first report of clinical features resulting from the Phe20Cys mutation in the SOD1 gene.