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

Journal Article · Wed Mar 01 04:00:00 EST 1995 · American Journal of Human Genetics

OSTI ID:70436

Pramatarova, A; Han, F Y; Rouleau, G A ^[1]; Figlewicz, D A ^[2]; Ceballos-Picot, I; Nicole, A; Meininger, V ^[3]; Grown, R H ^[4]

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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)

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.

• OSTI ID: 70436
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: 3 Vol. 56; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
AMINO ACID SEQUENCE
ENZYMES
GENE MUTATIONS
GENES
GENETIC MAPPING
HEREDITARY DISEASES
HUMAN CHROMOSOME 21
NERVOUS SYSTEM DISEASES
PATIENTS