Autosomal-Dominant Distal Myopathy Associated with a Recurrent Missense Mutation in the Gene Encoding the Nuclear Matrix Protein, Matrin 3

Senderek, Jan; Garvey, Sean M.; Krieger, Michael J. B.; Guergueltcheva, Velina; Urtizberea, Andoni; Roos, Andreas; Elbracht, Miriam; Stendel, Claudia; Tournev, Ivailo; Mihailova, Violeta; Feit, Howard; Tramonte, J.; Hedera, Peter; Crooks, Kristy; Bergmann, Carsten; Rudnik‐Schöneborn, Sabine; Zerres, Klaus; Lochmüller, Hanns; Seboun, Eric; Weis, Joachim; Beckmann, Jacques S.; Hauser, Michael A.; Jackson, Charles E.

doi:10.1016/j.ajhg.2009.03.006

Cited by 156 publications

(170 citation statements)

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“…Mutations in the valosin-containing protein (VCP) gene account for inclusion body myopathy with Paget's disease of bone and frontotemporal dementia (IBMFTD) and ALS 46,47 . Similarly mutations in MATRIN3 (MATR3) cause distal myopathy 48 and ALS 49 . Besides MSS manifesting as a vacuolar myopathy, there is also evidence for the involvement of motor neurons in MSS 50 .…”

Section: Discussionmentioning

confidence: 99%

Marinesco-Sjögren syndrome protein SIL1 regulates motor neuron subtype-selective ER stress in ALS

et al. 2015

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Mechanisms underlying motor neuron subtype-selective endoplasmic reticulum (ER) stress and associated axonal pathology in amyotrophic lateral sclerosis (ALS) remain unclear. Here we show that the molecular environment of the ER between motor neuron subtypes is distinct, with characteristic signatures. We identify cochaperone SIL1, mutated in Marinesco-Sjögren syndrome (MSS), as being robustly expressed in disease-resistant slow motor neurons but not in ER stress-prone fast-fatigable motor neurons. In a mouse model of MSS, we demonstrate impaired ER homeostasis in motor neurons in response to loss of SIL1 function. Loss of a single functional Sil1 allele in an ALS mouse model (SOD1-G93A) enhanced ER stress and exacerbated ALS pathology. In SOD1-G93A mice, SIL1 levels were progressively and selectively reduced in vulnerable fast-fatigable motor neurons. Mechanistically, reduction in SIL1 levels was associated with lowered excitability of fast-fatigable motor neurons, further influencing expression of specific ER chaperones. Adeno-associated virus-mediated delivery of SIL1 to familial ALS motor neurons restored ER homeostasis, delayed muscle denervation and prolonged survival.

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Section: Discussionmentioning

confidence: 99%

Marinesco-Sjögren syndrome protein SIL1 regulates motor neuron subtype-selective ER stress in ALS

et al. 2015

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“…1,2,3 One American patient was reported to be oxygen-dependent with restrictive pulmonary function. 1 Some of the German patients showed a decrease in vital capacity and complained of exertional dyspnea.…”

Section: Introductionmentioning

confidence: 98%

Impairment of respiratory function in late-onset distal myopathy due toMATR3Mutation

et al. 2015

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“…A mutation in MATR3 (S85C) was first identified as the cause of an autosomal dominant, distal, asymmetrical myopathy with vocal cord paralysis and pharyngeal weakness in a large North American multigenerational family (34) and in an unrelated Bulgarian family (96). Muscle biopsy disclosed a chronic noninflammatory myopathy with rimmed vacuoles, but features suggesting denervation were also detected, including presence of atrophic fibers.…”

Section: Distal Myopathy and Matr3mentioning

confidence: 97%

New ALS‐Related Genes Expand the Spectrum Paradigm of Amyotrophic Lateral Sclerosis

Sabatelli¹,

Marangi²,

Conte³

et al. 2016

Brain Pathology

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Amyotrophic Lateral Sclerosis (ALS) is characterized by the degeneration of upper and lower motor neurons. Clinical heterogeneity is a well-recognized feature of the disease as age of onset, site of onset and the duration of the disease can vary greatly among patients. A number of genes have been identified and associated to familial and sporadic forms of ALS but the majority of cases remains still unexplained. Recent breakthrough discoveries have demonstrated that clinical manifestations associated with ALS-related genes are not circumscribed to motor neurons involvement. In this view, ALS appears to be linked to different conditions over a continuum or spectrum in which overlapping phenotypes may be identified. In this review, we aim to examine the increasing number of spectra, including ALS/Frontotemporal Dementia and ALS/Myopathies spectra. Considering all these neurodegenerative disorders as different phenotypes of the same spectrum can help to identify common pathological pathways and consequently new therapeutic targets in these incurable diseases.

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Autosomal-Dominant Distal Myopathy Associated with a Recurrent Missense Mutation in the Gene Encoding the Nuclear Matrix Protein, Matrin 3

Cited by 156 publications

References 53 publications

Marinesco-Sjögren syndrome protein SIL1 regulates motor neuron subtype-selective ER stress in ALS

Marinesco-Sjögren syndrome protein SIL1 regulates motor neuron subtype-selective ER stress in ALS

Impairment of respiratory function in late-onset distal myopathy due toMATR3Mutation

New ALS‐Related Genes Expand the Spectrum Paradigm of Amyotrophic Lateral Sclerosis

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