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Title: Identification of new mutations in the Cu/Zn superoxide dismutase gene of patients with familial amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder affecting motor neurons. Although most cases of ALS are sporadic, {approximately}10% are inherited as an autosomal dominant trait. Mutations in the CU/An superoxide dismutase gene (SOD 1) are responsible for a fraction of familial ALS (FALS). Screening our FALS kindreds by SSCP, we have identified mutations in 15 families, of which 9 have not been previously reported. Two of the new mutations alter amino acids that have never been implicated in FALS. One of them affects a highly conserved amino acid involved in dimer contact, and the other one affects the active-site loop of the enzyme. These two mutations reduce significantly SOD 1 enzyme activity in lymphoblasts. Our results suggest that SOD 1 mutations are responsible for {>=}13% of FALS cases. 16 refs., 2 figs., 2 tabs.
Authors:
; ;  [1] ;  [2] ; ; ;  [3] ;  [4]
  1. McGill Univ., Montreal (Canada)
  2. Univ. of Rochester Medical Center, NY (United States)
  3. Centre de Diagnostic, Paris (France)
  4. Massachusetts General Hospital, Charlestown, MA (United States)
Publication Date:
OSTI Identifier:
70436
Resource Type:
Journal Article
Resource Relation:
Journal Name: American Journal of Human Genetics; Journal Volume: 56; Journal Issue: 3; Other Information: PBD: Mar 1995
Country of Publication:
United States
Language:
English
Subject:
55 BIOLOGY AND MEDICINE, BASIC STUDIES; GENES; GENE MUTATIONS; PATIENTS; NERVOUS SYSTEM DISEASES; HEREDITARY DISEASES; HUMAN CHROMOSOME 21; GENETIC MAPPING; ENZYMES; AMINO ACID SEQUENCE