Molecular genetic basis of familial ALS - PubMed (original) (raw)

Review

. 1996 Oct;47(4 Suppl 2):S27-34; discussion S34-5.

doi: 10.1212/wnl.47.4_suppl_2.27s.

Affiliations

Review

Molecular genetic basis of familial ALS

T Siddique et al. Neurology. 1996 Oct.

Abstract

Familial amytrophic lateral sclerosis (FALS) is transmitted in a mendelian fashion as an autosomal dominant (DFALS) or an autosomal recessive (RFALS) trait. Both DFALS and RFALS are genetically heterogeneous. Fifteen percent of DFALS families have mutations in the gene for Cu, Zn superoxide dismutase (SOD1) which is coded on chromosome 21. The locus for one form of RFALS maps to chromosome 2q33. Forty-six mutations in the SOD1 gene have been reported in DFALS families. These mutations result in decreased SOD1 activity and shortened half-life of the protein in most instances. Transgenic mice overexpressing mutated SOD1 protein develop an ALS-like disease which suggests that the degeneration of motor neurons in DFALS is caused by the gain of a novel toxic function by mutated SOD1 rather than by the decrease of SOD1 activity. Several possible mechanisms of the novel neurotoxic function of mutated SOD1 are discussed.

PubMed Disclaimer

Publication types

MeSH terms

Substances

LinkOut - more resources