Clustering of ALS patients in central Italy due to the occurrence of the L84F SOD1 gene mutation

Mauro Ceroni, A. Malaspina, T. E. Poloni, D. Alimonti, F. Rognoni, J. Habgood, F. Imbesi, P. Antonelli, E. Alfonsi, D. Curti, J. DeBelleroche

Research output: Contribution to journalArticle

Abstract

Objective: To study three new apparently unrelated Italian families with ALS and several sporadic ALS patients living in the same rural area. Background: One Italian family with ALS carrying a superoxide dismutase 1 (SOD1) gene mutation (G41S) and no regional ALS clustering has been reported in Italy. Methods: Genetic analysis was performed by automated and manual sequencing of the SOD1 gene in 13 family members and in 6 of 10 unrelated patients with sporadic cases of ALS living in the same area. The authors also determined SOD1 activity in erythrocytes and lymphocytes. Results: The three families included a total of 28 affected members distributed over six generations. Despite a wide variability in age at onset and disease duration, the clinical pattern is uniform, with onset in the lower limbs, ascending progression, and predominant lower motor neuron involvement in all subjects. Generational anticipation is evident in the last two generations. All familial ALS patients and one of the six sporadic patients carry the same L84F missense point mutation in exon 4 of the SOD1 gene. SOD1 enzyme activity and SOD1 protein levels were not decreased significantly in the L84F patients. Conclusion: The ALS patients carrying the L84F mutation derive from a common ancestor. This mutation is responsible for ALS clustering in the area. The L84F mutation does not modify SOD1-specific activity.

Original languageEnglish
Pages (from-to)1064-1071
Number of pages8
JournalNeurology
Volume53
Issue number5
Publication statusPublished - Sep 22 1999

Keywords

  • Familial ALS
  • Motor neuron disease
  • Pes cavus
  • SOD1 gene

ASJC Scopus subject areas

  • Neuroscience(all)

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    Ceroni, M., Malaspina, A., Poloni, T. E., Alimonti, D., Rognoni, F., Habgood, J., Imbesi, F., Antonelli, P., Alfonsi, E., Curti, D., & DeBelleroche, J. (1999). Clustering of ALS patients in central Italy due to the occurrence of the L84F SOD1 gene mutation. Neurology, 53(5), 1064-1071.