N19S, a new SOD1 mutation in sporadic amyotrophic lateral sclerosis: No evidence for disease causation

Mayeux, Véronique; Corcia, Philippe; Besson, Gérard; Jafari-Schluep, Helene-Farnase; Briolotti, Valérie; Camu, William

doi:10.1002/ana.10605

Cited by 18 publications

(7 citation statements)

References 14 publications

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“…ALS is a fatal degenerative disease characterized by progressive muscle weakness, paralysis and progressive loss of motor neurons (Charcot and Joffroy, 1869; Mayeux et al, 2003). Cases can be sporadic, where the inciting cause is unknown (~90% of cases), or familial, resulting from one of many genetic mutations.…”

Section: Respiratory Compromise In Cns Disordersmentioning

confidence: 99%

Common mechanisms of compensatory respiratory plasticity in spinal neurological disorders

Johnson

Mitchell

2013

Respiratory Physiology & Neurobiology

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In many neurological disorders that disrupt spinal function and compromise breathing (e.g. ALS, cervical spinal injury, MS), patients often maintain ventilatory capacity well after the onset of severe CNS pathology. In progressive neurodegenerative diseases, patients ultimately reach a point where compensation is no longer possible, leading to catastrophic ventilatory failure. In this brief review, we consider evidence that common mechanisms of compensatory respiratory plasticity preserve breathing capacity in diverse clinical disorders, despite the onset of severe pathology (e.g. respiratory motor neuron denervation and/or death). We propose that a suite of mechanisms, operating at distinct sites in the respiratory control system, underlies compensatory respiratory plasticity, including: 1) increased (descending) central respiratory drive, 2) motor neuron plasticity, 3) plasticity at the neuromuscular junction or spared respiratory motor neurons, and 4) shifts in the balance from more to less severely compromised respiratory muscles. To establish this framework, we contrast three rodent models of neural dysfunction, each posing unique problems for the generation of adequate inspiratory motor output: 1) respiratory motor neuron death, 2) de- or dysmyelination of cervical spinal pathways, and 3) cervical spinal cord injury, a neuropathology with components of demyelination and motor neuron death. Through this contrast, we hope to understand the multilayered strategies used to “fight” for adequate breathing in the face of mounting pathology.

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Section: Respiratory Compromise In Cns Disordersmentioning

confidence: 99%

Common mechanisms of compensatory respiratory plasticity in spinal neurological disorders

Johnson

Mitchell

2013

Respiratory Physiology & Neurobiology

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“…Five exon portions and flanking splice junctions of the SOD1 gene were amplified by PCR as previously described 9. Mutational analysis revealed a missense mutation in exon 5 (L144F) (figure 2).…”

Section: Sod1 Gene Analysismentioning

confidence: 99%

Respiratory onset in an ALS family with L144F SOD1 mutation

Corcia

Petiot

Stević

et al. 2010

Journal of Neurology, Neurosurgery & Psychiatry

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Familial amyotrophic lateral sclerosis (FALS) cases linked to SOD1 mutations may sometimes present with unusual clinical features such as pure lower motor neuron involvement or sensory signs. The authors describe a FALS pedigree with the L144F SOD1 mutation in which all cases had respiratory involvement as a first symptom. Although atypical clinical features are not rare in ALS families, this is the first pedigree with respiratory-onset in three affected members. This unusual presentation led to delayed diagnosis in the proband and highlights the fact that respiratory-onset can occur in familial ALS cases carrying SOD1 mutation.

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“…If one study supported a potential toxic effect of N19S on the survival of motor neurons and suggested it could be causative, more evidence is required to support a pathogenic role for this mutation due to the absence of co-segregation with the disease, as already suggested, and the lack of functional studies [1,3,4]. In view of the high proportion of C9orf72-linked ALS added to the growing literature supporting oligogenic inheritance, we considered it essential to screen the C9orf72 gene in our sample [5,6].…”

mentioning

confidence: 92%

“…To date, the pathogenicity of several mutations in the SOD1 gene remains uncertain due to the lack of evidence demonstrating the damage to motor neurons. This is the case for the N19S mutation for which no familial linkage has been shown [1,2]. However, the expression of this mutation in neural cell cultures leads to enhanced susceptibility to degeneration of these neural cells [3].…”

mentioning

confidence: 99%