ND10941

Overview

Repository

NINDS Repository

Subcollection

Motor Neuron Disease

Biopsy Source

Peripheral vein

Cell Type

B-Lymphocyte

Tissue Type

Blood

Transformant

Epstein-Barr Virus

Sample Source

LCL from B-Lymphocyte

Race

White

Subject Type

case-spouse

Family Type

NUCLEAR FAMILIES - ONE AFFECTED

Ethnicity

Not Hispanic/Latino

Ethnicity

Scottish

Country of Origin

USA

Family Member

Family History

Relation to Proband

proband

Species

Homo sapiens

Common Name

Human

Characterizations

Gene

SOD1

Chromosomal Location

21q22.11

Allelic Variant 1

147450.0011; AMYOTROPHIC LATERAL SCLEROSIS, FAMILIAL

Identified Mutation

ILE113THR; This mutation of the SOD1 gene was identified by Rosen et al. (1993) in a family with amyotrophic lateral sclerosis. The ile113-to-thr (I113T) substitution (an ATT to ACT basepair change) was found in 3 patients among 56 cases of ALS drawn from a population-based study in Scotland (Jones et al., 1993); all 3 were apparently the result of a new mutation, i.e., they represented sporadic ALS. Jones et al. (1993) suggested that sporadic cases of ALS may be due to de novo mutations or mutations of reduced penetrance. Jones et al. (1995) found the I113T mutation in 3 sporadic ALS cases and 3 unrelated familial cases of ALS in Scotland. Because of early death of parents of probands, together with illegitimacy in families, some of the apparently sporadic cases may, in fact, have been familial. The average age of onset of patients with the I113T mutation was cited as 61.2 years, with mean survival of 1.6 years. Hayward et al. (1996) reported 6 additional cases in Scotland with the I113T mutation and the same genetic background (haplotype) despite no evidence of relatedness. Brock (1998) reported that he and his coworkers had found another 3 cases in the north of England with the I113T mutation and the identical genetic background, one that is rare in the general population. In a disorder such as ALS in which environmental factors may interact with the genotype, or indeed other genes interact with the SOD1 gene, the finding is expected. Kikugawa et al. (1997) performed mutational analyses of the SOD1 gene of 23 patients (3 familial and 20 sporadic) with ALS from the Kii Peninsula of Japan and its vicinity, where a relatively high incidence of familial occurrence of ALS had been observed. In 2 of the 23 patients, they identified heterozygosity for the I113T mutation in exon 4. The I113T mutation had been identified in some familial as well as sporadic cases of ALS as a mutation with low penetrance. The mutation had been reported to be associated with the formation of neurofibrillary tangles and such was a characteristic feature of ALS in the Kii Peninsula.

Publications

Cunha-Oliveira T, Silva DF, Segura L, Baldeiras I, Marques R, Rosenstock T, Oliveira PJ, Silva FSG, Redox profiles of amyotrophic lateral sclerosis lymphoblasts with or without known SOD1 mutations European journal of clinical investigation52:e13798 2022

PubMed ID: 35467758

External Links

NCBI GTR

105400 AMYOTROPHIC LATERAL SCLEROSIS 1; ALS1

OMIM

105400 AMYOTROPHIC LATERAL SCLEROSIS 1; ALS1

Omim Description

ALS

AMYOTROPHIC LATERAL SCLEROSIS

AMYOTROPHIC LATERAL SCLEROSIS, TYPE 1; ALS1

Images

View

pedigree

Culture Protocols

Split Ratio (Frequency)

1:3 (4 Days)

Temperature

37 C

Percent CO2

Percent O2

AMBIENT

Medium

Roswell Park Memorial Institute Medium 1640 with 2mM L-glutamine or equivalent

Serum

15% fetal bovine serum Not Inactivated

Substrate

None specified

Subcultivation Method

dilution - add fresh medium

Supplement

Description:

AMYOTROPHIC LATERAL SCLEROSIS 1; ALS1

Affected:

Yes

Gender:

Male

Age:

46 YR (At Sampling)