Molecular genetic basis of familial ALS

Teepu Siddique, Deepak Nijhawan, Afif Hentati

Research output: Contribution to journalArticle

91 Citations (Scopus)

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.

Original languageEnglish (US)
JournalNeurology
Volume47
Issue number4 SUPPL.
StatePublished - Oct 1996

Fingerprint

Molecular Biology
Mutation
Chromosomes, Human, Pair 21
Motor Neuron Disease
Poisons
Motor Neurons
Transgenic Mice
Genes
Half-Life
Chromosomes
Proteins
Superoxide Dismutase-1

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Siddique, T., Nijhawan, D., & Hentati, A. (1996). Molecular genetic basis of familial ALS. Neurology, 47(4 SUPPL.).

Molecular genetic basis of familial ALS. / Siddique, Teepu; Nijhawan, Deepak; Hentati, Afif.

In: Neurology, Vol. 47, No. 4 SUPPL., 10.1996.

Research output: Contribution to journalArticle

Siddique, T, Nijhawan, D & Hentati, A 1996, 'Molecular genetic basis of familial ALS', Neurology, vol. 47, no. 4 SUPPL..
Siddique T, Nijhawan D, Hentati A. Molecular genetic basis of familial ALS. Neurology. 1996 Oct;47(4 SUPPL.).
Siddique, Teepu ; Nijhawan, Deepak ; Hentati, Afif. / Molecular genetic basis of familial ALS. In: Neurology. 1996 ; Vol. 47, No. 4 SUPPL.
@article{b3998c1093f0448c9c1a650ff7ef46e4,
title = "Molecular genetic basis of familial ALS",
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.",
author = "Teepu Siddique and Deepak Nijhawan and Afif Hentati",
year = "1996",
month = "10",
language = "English (US)",
volume = "47",
journal = "Neurology",
issn = "0028-3878",
publisher = "Lippincott Williams and Wilkins",
number = "4 SUPPL.",

}

TY - JOUR

T1 - Molecular genetic basis of familial ALS

AU - Siddique, Teepu

AU - Nijhawan, Deepak

AU - Hentati, Afif

PY - 1996/10

Y1 - 1996/10

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0029808008&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029808008&partnerID=8YFLogxK

M3 - Article

C2 - 8858048

AN - SCOPUS:0029808008

VL - 47

JO - Neurology

JF - Neurology

SN - 0028-3878

IS - 4 SUPPL.

ER -