Adult onset neurodegenerative disorder
Gene: SOD1The mode of inheritance of this gene has been updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.Created: 1 Feb 2023, 12:22 p.m. | Last Modified: 1 Feb 2023, 12:22 p.m.
Panel Version: 3.49
MOI should be changed from "MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown" to "BOTH monoallelic and biallelic, autosomal or pseudoautosomal".
PMID: 7647793 identified homozygous variants in SOD1 in 14 affected people from 4 unrelated families (some were consanguineous) from Sweden or Finland with ALS. All affected individuals are homozgyous for the the same variant (D90A). Heterozygous carriers were not affected.
PMID: 9817920 studied 28 pedigrees with D90A from around the world. The authors found that 20 recessive familes have the same founder haplotype as
PMID:7647793, regardless of location, and that heterozygous carriers in these families were also unaffected. In the dominant families, 5 were sporadic (no family history of ALS) and 3 were familial and several founders existed for these families. This study shows that D90A can cause disease in a dominant fashion just like all other SOD1 variants. Recessive inheritance of ALS caused by D90A has also been reported in families from Russia, Germany, Iran, Italy, France, Australia, Canada, and US (PMID: 18608106, 10809943, 12442272, 11284995, 11127534, 23062701).
PMID: 11220750 identified a French family with ALS, where the affected individuals were compound heterozygous for D90A and D96N in SOD1.Created: 1 Sep 2021, 9:18 a.m. | Last Modified: 1 Sep 2021, 9:18 a.m.
Panel Version: 2.195
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications
Amyotrophic lateral sclerosis is a neurodegenerative disorder characterized by the death of motor neurons in the brain, brainstem, and spinal cord, resulting in fatal paralysis. Adult-onset - > 3 casesCreated: 2 Sep 2019, 4:06 p.m. | Last Modified: 2 Sep 2019, 4:06 p.m.
Panel Version: 1.99
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Amyotrophic lateral sclerosis 1, 105400; amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis, Dominant
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Amyotrophic lateral sclerosis 1, 105400; amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis, Dominant
Publications
Variants in this GENE are reported as part of current diagnostic practice
Review and rating from Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group. All the green and amber, except for the genes with triplet repeats, were reviewed.Created: 2 Sep 2019, 4:46 p.m. | Last Modified: 2 Sep 2019, 4:46 p.m.
Panel Version: 1.101
Review and rating submitted by Nick Beauchamp (Sheffield Diagnostic genetics Service), on behalf of Yorkshire and North East GLH for GMS Neurology specialist test group.Created: 23 Jul 2019, 3:51 p.m. | Last Modified: 23 Jul 2019, 3:51 p.m.
Panel Version: 1.74
Review and rating submitted byJames Polke (North Bristol NHS Trust), unless specified in the review comment, on behalf of London North GLH for GMS Neurology specialist test group.Created: 23 Apr 2019, 5:35 p.m.
Variants in this GENE are reported as part of current diagnostic practice
Tag Q3_21_MOI was removed from gene: SOD1.
Mode of inheritance for gene SOD1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SOD1 were set to 23687121; 24501761; 25439728
Tag Q3_21_MOI tag was added to gene: SOD1.
Phenotypes for gene: SOD1 were changed from Amyotrophic lateral sclerosis 1, 105400; amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis, Dominant to Amyotrophic lateral sclerosis 1, OMIM:105400
Source Wessex and West Midlands GLH was added to SOD1.
Publications for gene SOD1 were changed from 23687121 to 23687121; 24501761; 25439728
Source Yorkshire and North East GLH was added to SOD1.
Source NHS GMS was added to SOD1.
Source London North GLH was added to SOD1.
Louise Daugherty: Comment on phenotypes: amended
Mode of pathogenicity for gene: SOD1 was changed from to Other
gene: SOD1 was added gene: SOD1 was added to Neurodegenerative disorders - adult onset. Sources: Expert Review Green Mode of inheritance for gene: SOD1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: SOD1 were set to 23687121 Phenotypes for gene: SOD1 were set to Amyotrophic lateral sclerosis 1, 105400; amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis, Dominant