| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
From the Department of Neuroscience (Drs. Ceroni, Malaspina, Poloni, Alimonti, Imbesi, and Alfonsi), "Istituto Neurologico C Mondino," Laboratory of Neurogenetics; the Department of Pharmacology (Drs. Rognoni and Curti), University of Pavia, Italy; the Department of Neuromuscular Diseases (Drs. Malaspina, Habgood, and deBelleroche), Division of Neuroscience and Psychological Medicine, Imperial College School of Medicine, Charing Cross Hospital, London, UK; and the Department of Rehabilitation (Dr. Antonelli), "Comunita’ di Capodarco" Capodarco, Ascoli Piceno, Italy.
Address correspondence and reprint requests to Dr. Mauro Ceroni, Department of Neurological Science, "Istituto Neurologico C Mondino," via Palestro 3, 27100 Pavia, Italy; e-mail: mceroni{at}unipv.it
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.
Key words: Familial ALS—SOD1 gene—Pes cavus—Motor neuron disease.
This article has been cited by other articles:
|
|
 |
|
  A. Chio, B. J. Traynor, F. Lombardo, M. Fimognari, A. Calvo, P. Ghiglione, R. Mutani, and G. Restagno Prevalence of SOD1 mutations in the Italian ALS population Neurology, February 12, 2008; 70(7): 533 - 537. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Bradley, L. Bradley, J. de Belleroche, and R. W. Orrell Patterns of inheritance in familial ALS Neurology, May 10, 2005; 64(9): 1628 - 1631. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S Niemann, H Joos, T Meyer, S Vielhaber, U Reuner, M Gleichmann, R Dengler, and U Muller Familial ALS in Germany: origin of the R115G SOD1 mutation by a founder effect J. Neurol. Neurosurg. Psychiatry, August 1, 2004; 75(8): 1186 - 1188. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. E. Sabel, P. J. Boyle, M. Loytonen, A. C. Gatrell, M. Jokelainen, R. Flowerdew, and P. Maasilta Spatial Clustering of Amyotrophic Lateral Sclerosis in Finland at Place of Birth and Place of Death Am. J. Epidemiol., May 15, 2003; 157(10): 898 - 905. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K Iwai, M Yamamoto, T Yoshihara, and G Sobue Anticipation in familial amyotrophic lateral sclerosis with SOD1-G93S mutation J. Neurol. Neurosurg. Psychiatry, June 1, 2002; 72(6): 819 - 820. [Full Text] [PDF]
|
|
|
|
 |
|
 L. P. Rowland and N. A. Shneider Amyotrophic Lateral Sclerosis N. Engl. J. Med., May 31, 2001; 344(22): 1688 - 1700. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
