Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
 19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent genetic analyses of patients with a familial, chromosome 21-linked form of amyotrophic lateral sclerosis (ALS), sometimes called Lou Gehrig's disease, suggest that mutations in the cytosolic copper/zinc superoxide dismutase (SOD1) gene may be involved in development of the disease. Although no functional disturbance of SOD1 activity has yet been identified, altered free radical protection may contribute to the destruction of motor neurons. The role of antioxidant status needs to be investigated as a possible preventive and therapeutic intervention for ALS.
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PMID:Mutations in the copper- and zinc-containing superoxide dismutase gene are associated with "Lou Gehrig's disease". 830 96

We have discovered a new Italian pedigree with autosomal-dominant ALS. The pedigree, at present, comprises 75 members distributed in five generations. ALS was diagnosed in eight patients. The mean +/- SD age of onset of the disease was 46.8 +/- 13.5 years, with a range of 29 to 63 years. The mean +/- SD duration of the disease was 11.6 +/- 1.7 months. Molecular genetic studies showed a missense mutation (Gly-->Ser, codon 41) in exon 2 of the Cu/Zn superoxide dismutase gene (SOD1) on chromosome 21 in the available affected member and in 45% of the at-risk subjects of the pedigree. This study confirms the presence of SOD1 point mutations in families with autosomal-dominant ALS and suggests that additional genetic or environmental factors may be involved in the full expression of the disease.
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PMID:SOD1 missense mutation in an Italian family with ALS. 830 90

Receptors for the major excitatory neurotransmitter glutamate may play key roles in neurodegeneration. The mouse Glur-5 gene maps to chromosome 16 between App and Sod-1. The homologous human GLUR5 gene maps to the corresponding region of human chromosome 21, which contains the locus for familial amyotrophic lateral sclerosis. This location, and other features, render GLUR5 a possible candidate gene for familial amyotrophic lateral sclerosis. In addition, dosage imbalance of GLUR5 may have a role in the trisomy 21 (Down syndrome). Further characterization of the murine glutamate receptor family includes mapping of Glur-1 to the same region as neurological mutants spasmodic, shaker-2, tipsy, and vibrator on chromosome 11; Glur-2 near spastic on chromosome 3; Glur-6 near waltzer and Jackson circler on chromosome 10; and Glur-7 near clasper on chromosome 4.
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PMID:Chromosomal localization of glutamate receptor genes: relationship to familial amyotrophic lateral sclerosis and other neurological disorders of mice and humans. 846 23

Familial amyotrophic lateral sclerosis (FALS) has recently been shown to be linked to chromosome 21 markers in a subset of families. However, we were unable to show linkage between FALS and chromosome 21 markers which flank the putative FALS locus in UK families.
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PMID:Absence of linkage between chromosome 21 loci and familial amyotrophic lateral sclerosis. 848 80

A family with autosomal-dominant amyotrophic lateral sclerosis with histopathological confirmation on autopsy was described. A 42-year-old female proband showed the signs and symptoms only in the lower limbs characteristic of lower motor neuron involvement at the onset. ALS had been diagnosed in other five members in three generations of her family. The mean +/- SD age of onset of the disease was 42.5 +/- 9.3 years with a range of 30 to 51 years. The mean +/- SD duration of the disease (n = 5, excluding the proband) was 56 +/- 70 months with a range of 7 to 180 months. Molecular genetic studies showed a T-to-G transversion that results in the substitution of valine for leucine84 in exon 4 of the Cu/Zn superoxide dismutase (SOD) gene on chromosome 21 in a proband. This mutation is identical to that found in the Japanese family with autosomal-dominant ALS characterized by short duration of the disease, within 1.5 years, in all the affected family members. Therefore, the clinical phenotype, especially the duration of the disease seems to be highly variable even in the families with the identical mutation of the Cu/Zn SOD gene.
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PMID:[Familial amyotrophic lateral sclerosis showing variable clinical courses with (Leu84-->Val) mutation of Cu/Zn superoxide dismutase]. 874 55

Amyotrophic lateral sclerosis is a fatal neurodegenerative disorder affecting primarily upper and lower motor neurons. In all cases of ALS, approximately 5-10% of cases are familial (FALS). Missense mutations in the Cu/Zn superoxide dismutase (SOD1) gene on chromosome 21 have been demonstrated in some families of FALS since 1993. We have also identified a novel missense mutation (substitution of Thr for Ala4) in exon 1 in a Japanese FALS family, and clarified the pathological findings of a patient in this family were typical of FALS with posterior column involvement. However, the mechanism by which the mutations in SOD1 lead to ALS is unknown. It is now clear that the mutations in SOD1 reduce total SOD activities only by 30-60%, and there is doubt whether a reduction in enzymatic function of this magnitude suffices to cause the neuronal loss. Recently, transgenic mice expressing the mutant SOD1 demonstrate motor neuron degeneration despite an increased level of SOD activity. The process of motor neuron degeneration in FALS might be mediated by some novel functions of the mutant SOD1 protein.
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PMID:[Familial amyotrophic lateral sclerosis and mutations in the Cu/Zn superoxide dismutase gene]. 875 59

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.
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PMID:Molecular genetic basis of familial ALS. 885 48

Amyotrophic lateral sclerosis (ALS) is inherited in ten percent of cases as a Mendelien trait. Familial ALS (FALS) is genetically heterogeneous and transmitted either as an autosomal dominant (DFALS) or an autosomal recessive (RFALS) trait. Fifteen percent of DFALS families have mutations in the gene for Cu,Zn superoxide dismutase (SOD1) which is coded on chromosome 21. These mutations result in decreased SOD1 activity and shortened half-life of the protein in most instances. Several observations suggest 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. Possible mechanisms of the novel neurotoxic function of mutated SOD1 are discussed. The role of eventual neurofilament involvement in the pathogenesis of ALS is also discussed. The locus for one form of RFALS has been mapped to chromosome 2q33. FALS can also be associated with dementia and the gene locus for one form of hereditary ALS-dementia syndrome maps to chromosome 17q21-22.
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PMID:Familial amyotrophic lateral sclerosis. 902 Dec 55

We report on an Austrian pedigree with autosomal dominant amyotrophic lateral sclerosis (ALS), diagnosed in six patients from two generations. The only surviving clinically affected family member was examined in our ALS clinic. Historical information on other affected individuals was obtained from knowledgeable family members. The mean +/- S.D. age of onset of the disease was 54 +/- 6.9 years, with a range of 43-66 years. The duration of the index patient's disease until death was 8 months. Using single strand conformational polymorphism (SSCP) analysis, we studied the index patient's exons 1, 2 and 4 of the Cu/Zn superoxide dismutase gene (SOD1) on chromosome 21. A variant banding pattern was observed for exon 1. Sequencing studies showed a previously undescribed T to A missense mutation at position 8 in exon 1 of the SOD1 gene. This mutation results in the elimination of an Eco57I restriction site. Whereas the index patient was heterozygous for this restriction site, 50 unrelated healthy controls and an unaffected brother were not. The mutation lies in a region involved in dimer contact in the three-dimensional structure of the SOD1 protein. This region comprises other known sites for ALS-causing mutations.
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PMID:A novel SOD1 mutation in an Austrian family with amyotrophic lateral sclerosis. 913 52

Amyotrophic lateral sclerosis is sporadic in ninety percent of cases and familial (FALS) in ten percent. Both forms of FALS whether transmitted as an autosomal dominant (DFALS) or as an autosomal recessive (RFALS) trait is genetically heterogeneous. The locus for one form of RFALS maps to chromosome 2q33. Fifteen percent of DFALS families have mutations in the gene for Cu, Zn superoxide dismutase (SOD1) gene which is coded on chromosome 21. 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. Possible mechanisms of the novel neurotoxic function of mutated SOD1 are discussed.
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PMID:Familial amyotrophic lateral sclerosis. 926 31


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