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A familial ALS case carrying a novel p.G147C SOD1 heterozygous missense mutation with non-executive cognitive impairment
  1. Antonio Canosa1,2,
  2. Andrea Calvo1,
  3. Cristina Moglia1,
  4. Barbara Iazzolino1,
  5. Maura Brunetti3,
  6. Gabriella Restagno3,
  7. Angelina Cistaro4,
  8. Piercarlo Fania4,
  9. Giovanna Carrara5,
  10. Maria Consuelo Valentini5,
  11. Raffaella Tanel6,
  12. Adriano Chiò1,7
  1. 1‘Rita Levi Montalcini’ Department of Neuroscience, ALS Center, University of Turin, Turin, Italy
  2. 2Department of Neurosciences, Ophthalmology, Genetics, Rehabilitation and Child Health, University of Genoa, Genoa, Italy
  3. 3Laboratory of Molecular Genetics, A.O.U. Città della Salute e della Scienza di Torino, Turin, Italy
  4. 4Department of Nuclear Medicine, Positron Emission Tomography Centre, IRMET S.p.A., Turin, Italy
  5. 5Department of Neuroradiology, A.O.U. Città della Salute e della Scienza di Torino, Turin, Italy
  6. 6Unità Operativa di Neurologia, Presidio Ospedaliero Santa Chiara, APSS di Trento, Trento, Italy
  7. 7Neuroscience Institute of Turin, Turin, Italy
  1. Correspondence to Professor Adriano Chiò, ‘Rita Levi Montalcini’ Department of Neuroscience, ALS Center, University of Torino, via Cherasco 15, Torino 10126, Italy; achio{at}usa.net

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Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease causing progressive muscle weakness and wasting. Death usually occurs within 3–5 years from respiratory failure. Approximately 10% of cases are familial (fALS).The frequency of SOD1 gene mutations in patients with fALS varies among populations, from 0% in Ireland to 13.6% in Italy and 23.5% in Scandinavia.1 SOD1 encodes for the Cu/Zn Superoxide Dismutase 1. Mutations are usually autosomal dominant, but the p.D90A and the p.D96N may be autosomal recessive.2

Performing the genetic screening of an Italian fALS series, we found a novel c.442g>t heterozygous missense mutation of SOD1 gene leading to a substitution of cysteine for glycine (p.G147C). Such mutation was absent in healthy controls (n=130). The patient provided written informed consent.

The index case displayed progressive weakness and wasting of both hands when he was 52 years old. One year after the onset he also exhibited tongue hypotrophy with fasciculations, spastic paraparesis, impairment of feet extension and brisk jaw jerk and lower limbs reflexes. Plantar response was absent bilaterally. He referred diffuse cramps and fasciculations. Dysphagia, dysarthria, dysphonia and dyspnoea were absent. The amyotrophic lateral sclerosis funcional rating scale revised (ALSFRS-R) was 44/48. Needle electromyography (EMG) showed chronic and active denervation in bulbar and spinal regions. Forced vital capacity was 106%. The neuropsychological evaluation showed an impaired performance in the Rey-Osterrieth Complex Figure (ROCF) Test, in copy and recall task, while other tests had normal scores. Brain MRI showed selective atrophy of the right supramarginal gyrus (figure 1 …

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