Les anomalies du gène superoxyde dismutase 1 dans la sclérose latérale amyotrophique familiale : corrélations phénotype/génotype et implications pratiques. L’expérience française et revue de la littérature

doi:10.1016/S0035-3787(04)70846-2

Revue Neurologique

Volume 160, Issue 1, January 2004, Pages 44-50

https://doi.org/10.1016/S0035-3787(04)70846-2 Get rights and content

Résumé

La sclérose latérale amyotrophique familiale (SLAF) représente 20 p. 100 des cas de SLA. Dans 15 p. 100 des SLAF, une anomalie du gène codant pour la superoxyde dismutase 1 (SOD1) est retrouvée. Pour la majorité d’entre elles, il s’agit d’une mutation ponctuelle, avec remplacement d’un nucléotide par un autre. La transmission est autosomique dominante pour toutes les anomalies génétiques sauf deux, qui sont récessives. À ce jour, plus de 100 anomalies génétiques différentes sont rapportées. Le profil clinique caractéristique des SLAF associées aux mutations SOD1 est homogène lorsque le lien entre la mutation et la maladie est clairement établi : âge moyen de début à 42 ans, début aux membres, évolution lente. En dehors d’un caractère familial dominant (plusieurs sujets atteints sur plusieurs générations), la causalité de la mutation est souvent discutable, ne justifiant pas une recherche systématique de mutation SOD1 devant une SLA atypique (début très jeune, évolution très longue, par exemple). Hormis dans le cas des quelques mutations fréquentes et prouvées causales (moins de 15 sur plus de 90), la multiplicité des mutations, la variabilité de leur mode de transmission et le caractère souvent discutable de leur responsabilité dans la maladie, justifient l’étude la plus complète possible d’une famille afin d’établir la causalité de l’anomalie génétique retrouvée ainsi que sa transmission.

Summary

About 20 p. cent of cases of amyotrophic lateral sclerosis are familial (FALS). Fifteen percent of FALS cases are associated with an abnormality in the superoxide dismutase 1 (SOD1) gene. To date, more than 100 different genetic abnormalities have been reported, all except two are autosomal dominant. The clinical characteristics of patients presenting with FALS associated with an SOD1 abnormality is homogeneous when there is no doubt about the hereditary aspect of the genetic abnormality: mean age at onset 42 years, limb onset, slow evolution. Except when present in the setting of a clearly inherited disease (FALS) (several patients through several generations), the causality of a given SOD1 mutation often remains an open question. Consequently, search for SOD1 mutation is not warranted when atypical features such as young age at onset or slow progression are present. Conversely, a complete family study is justified to determine the precise role of a given SOD1 mutation because of the large number of potential SOD1 mutations, the variability of the transmission mode, and the non-exceptional absence of proven causality for ALS. Specific cases where a frequent SOD1 mutation with a recognized causal effect is recognized (no more than 15 out of more than 90 mutations) would be an exception.

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Mutational analysis of the Cu/Zn superoxide dismutase gene in a Catalan ALS population: Should all sporadic ALS cases also be screened for SOD1?
2006, Journal of the Neurological Sciences
SOD1 gene mutations are the most common identified cause of ALS, accounting for approximately 20% of familial ALS cases and around 4% of sporadic ALS cases. However, the prevalence of SOD1 varies in different ethnic groups. No previous epidemiological studies have been carried out in Catalonia.
To determine the prevalence of SOD1 gene mutations in a Catalan ALS population, and to analyze the genotype-phenotype relationship.
30 different FALS pedigrees and 94 sporadic ALS patients were screened for SOD1 mutations using direct sequence analysis.
Five of the 30 FALS pedigrees (16.6%) carried a SOD1 mutant. The mutations identified in this group were G37R, D76V, S105L, I112M and N139H. Four SOD1 mutants (4.25%) were found in the sporadic ALS group (SALS). The overall frequency (FALS plus SALS) of SOD1 mutations in our series was 6.45%. In the SALS group, D90A was identified in a patient presenting the typical Scandinavian phenotype. A 53-year-old woman with no family history of ALS carried the N139H mutation. Two unrelated sporadic ALS cases carried the A140A SOD1 mutant.
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Résumé

Summary

Cell

Neurosci Lett

J Neurol sci

Neurobiol Dis

Recessive amyotrophic lateral sclerosis families with the D90A SOD1 mutation share a common founder: evidence for a linked protective factor

Hum Mol Genet

Genetics of Sporadic ALS

Amyotroph Lateral Scler Other Motor Neuron Disord

Autosomal recessive adult-onset amyotrophic lateral sclerosis associated with homozygosity for Asp90Ala Cu, Zn superoxide dismutase mutation. A clinical and genealogical study of 36 patients

Brain

Mild ALS in Japan associated with novel SOD mutation

Nat Genet

Recherches sur une maladie non encore décrite du système musculaire

Arch Gen Med

Superoxide dismutase 1 with mutations linked to familial ALS possesses significant activity

Proc Natl Acad Sci

Identification of six novel SOD1 gene mutations in familial ALS patients

Can J Neurol Sci

Clustering of ALS patients in central Italy due to the occurrence of the L84F SOD1 gene mutation

Neurology

Limited corticospinal Tract Involvement in ALS subjects with the A4V mutation in the Cu/Zn SOD1 gene

Ann Neurol

Epidemiology of mutations in SOD in ALS

Ann Neurol

ALS and structural defects in Cu, Zn SOD

Science

Identification of two novel mutaions and a new polymorphism in the gene for Cu/Zn SOD in pateints with ALS

Hum Mol Genet