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ALS patients with SOD1 mutations in Switzerland show very diverse phenotypes and extremely long survival
  1. M Weber1,2,
  2. C Neuwirth1,
  3. J Thierbach3,
  4. K Schweikert2,
  5. A Czaplinski2,
  6. J Petersen4,
  7. H H Jung4,
  8. A Birve5,
  9. S L Marklund6,
  10. P M Andersen5
  1. 1Neuromuscular Diseases Unit/ALS Clinic, Kantonsspital St. Gallen, St. Gallen Switzerland
  2. 2Department of Neurology, University Hospital Basel, Basel, Switzerland
  3. 3Red Cross Blood Donation Center, St. Gallen, Switzerland
  4. 4Department of Neurology, University Hospital Zürich, Zürich Switzerland
  5. 5Institute of Clinical Neuroscience, Umeå University, Umeå, Sweden
  6. 6Institute of Biomedical Sciences, Umeå University, Umeå, Sweden
  1. Correspondence to Markus Weber, MD, Neuromuscular Diseases Unit, Kantonsspital St.Gallen, 9007 St. Gallen, Switzerland; markus.weber{at}kssg.ch

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Introduction

Familial amyotrophic lateral sclerosis (FALS) is recognised as a heterogeneous syndrome with mutations in the Cu/Zn superoxide dismutase (SOD1) gene being the most frequently identified cause of ALS. Interfamily and intrafamily phenotypic variability have been associated with some SOD1 mutations but not with other mutations.1 2 We prospectively screened sporadic ALS and FALS patients from Switzerland for SOD1 mutations and followed their clinical course.

Methods

With written informed consent and approval by the local ethical review boards, blood was drawn from 257 patients and from 245 Swiss blood donors matched for ethnicity, age and gender. Forty-seven of the patients had one or more affected blood relatives within three generations and were classified as FALS. SOD1 analysis was performed in Sweden as described.1

Results

Nine patients from seven unrelated families carried a SOD1 mutation (table 1), including three novel mutations (V5L, L144F (TTG→TTT) and E78insSI (c.240-7T→G)). Among the controls, a single individual was found to be heterozygous for a silent mutation A140A.

View this table:
Table 1

Main clinical aspects of the patients with SOD1 gene mutations

Selected phenotypic depictions of patients with SOD1 mutations

L144F (TTG→TTT)

In 1962, at the age of 28 years, the patient (2a) noticed weakness in her legs and was diagnosed as having Friedreich ataxia in the same year and spinal muscular atrophy 5 years later. She became a wheelchair user 28 years after symptom onset. A percutaneous endoscopic gastrostomy tube was inserted and …

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