Re-evaluation of the phenotype caused by the common<i>MATR3</i>p.Ser85Cys mutation in a new family

Palmio, Johanna; Evilä, Anni; Bashir, Ayat; Norwood, Fiona; Viitaniemi, Kati; Vihola, Anna; Huovinen, Sanna; Straub, Volker; Hackman, Peter; Hirano, Michio; Bushby, Kate; Udd, Bjarne

doi:10.1136/jnnp-2014-309349

Cited by 30 publications

(29 citation statements)

References 12 publications

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“…Many groups have reported gastrocnemius or tibialis anterior muscle containing fibers of variable size, increased subsarcolemmal nuclei, and the presence of vacuoles in affected individuals with Matrin 3 mutations, similar to that observed in our phenotypic mice in the context of wild-type Matrin 3 [6, 16, 18, 27, 34]. The robust increase in Matrin 3 levels within the skeletal muscle of our Tg lines could suggest that any increase in normal levels or function of the protein in the muscle is responsible for the mouse phenotype.…”

Section: Discussionsupporting

confidence: 86%

“…The pathology that we observed in the Matrin 3 Tg mice appears to closely resemble that from distal myopathy cases with Matrin 3 mutation [6, 16, 18, 27, 34]. Many groups have reported gastrocnemius or tibialis anterior muscle containing fibers of variable size, increased subsarcolemmal nuclei, and the presence of vacuoles in affected individuals with Matrin 3 mutations, similar to that observed in our phenotypic mice in the context of wild-type Matrin 3 [6, 16, 18, 27, 34].…”

Section: Discussionmentioning

confidence: 92%

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RETRACTED ARTICLE: Transgenic mice overexpressing the ALS-linked protein Matrin 3 develop a profound muscle phenotype

Moloney

Rayaprolu

Howard

et al. 2016

acta neuropathol commun

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Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder of upper and lower motor neurons. Mutations in the gene encoding the nuclear matrix protein Matrin 3 have been found in familial cases of ALS, as well as autosomal dominant distal myopathy with vocal cord and pharyngeal weakness. We previously found that spinal cord and muscle, organs involved in either ALS or distal myopathy, have relatively lower levels of Matrin 3 compared to the brain and other peripheral organs in the murine system. This suggests that these organs may be vulnerable to any changes in Matrin 3. In order to determine the role of Matrin 3 in these diseases, we created a transgenic mouse model for human wild-type Matrin 3 using the mouse prion promoter (MoPrP) on a FVB background.We identified three founder transgenic lines that produced offspring in which mice developed either hindlimb paresis or paralysis with hindlimb and forelimb muscle atrophy. Muscles of affected mice showed a striking increase in nuclear Matrin 3, as well as the presence of rounded fibers, vacuoles, nuclear chains, and subsarcolemmal nuclei. Immunoblot analysis of the gastrocnemius muscle from phenotypic mice showed increased levels of Matrin 3 products migrating at approximately 120 (doublet), 90, 70, and 55 kDa. While there was no significant change in the levels of Matrin 3 in the spinal cord in the phenotypic mice, the ventral horn contained individual cells with cytoplasmic redistribution of Matrin 3, as well as gliosis. The phenotypes of these mice indicate that dysregulation of Matrin 3 levels is deleterious to neuromuscular function.Electronic supplementary materialThe online version of this article (doi:10.1186/s40478-016-0393-5) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 92%

RETRACTED ARTICLE: Transgenic mice overexpressing the ALS-linked protein Matrin 3 develop a profound muscle phenotype

Moloney

Rayaprolu

Howard

et al. 2016

acta neuropathol commun

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“…Weakness of the index finger extensors (similarly to that observed in TIA1‐myopathy) and weakness and atrophy of the first dorsal interosseous and thenar muscles, with relative sparing of the abductor digiti minimi, can be prominent . Similarly to other myopathies, matrin‐3‐myopathy has phenotypic variability: proximal weakness can be the presenting symptom and vocal cord and pharyngeal weakness can be a mild or later symptom . Respiratory insufficiency is common, sometimes resulting in need for respiratory support .…”

Section: Distal Myopathy/motor Neuron Disease Multisystem Proteinopamentioning

confidence: 92%

“…Electromyography (EMG) findings include motor unit potentials with short duration and reduced amplitude, early recruitment, fibrillation potentials and complex repetitive discharges . Muscle biopsy in most cases shows rimmed vacuoles and nuclei with abnormal invaginations, as seen by electron microscopy, although some biopsies may reveal only mild nonspecific myopathic changes . Matrin‐3 immunoreactivity can be lacking in the central region of the myonuclei.…”

Section: Distal Myopathy/motor Neuron Disease Multisystem Proteinopamentioning

confidence: 99%

The unfolding spectrum of inherited distal myopathies

Milone

Liewluck

2018

Muscle and Nerve

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Distal myopathies are a group of rare muscle diseases characterized by distal weakness at onset. Although acquired myopathies can occasionally present with distal weakness, the majority of distal myopathies have a genetic etiology. Their age of onset varies from early-childhood to late-adulthood while the predominant muscle weakness can affect calf, ankle dorsiflexor, or distal upper limb muscles. A spectrum of muscle pathological changes, varying from nonspecific myopathic changes to rimmed vacuoles to myofibrillar pathology to nuclei centralization, have been noted. Likewise, the underlying molecular defect is heterogeneous. In addition, there is emerging evidence that distal myopathies can result from defective proteins encoded by genes causative of neurogenic disorders, be manifestation of multisystem proteinopathies or the result of the altered interplay between different genes. In this review, we provide an overview on the clinical, electrophysiological, pathological, and molecular aspects of distal myopathies, focusing on the most recent developments in the field. Muscle Nerve, 2018.

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“…In 16 German patients from 6 families, harboring the S85C MATR3 mutation, muscle biopsy showed only myopathic changes, including variation of fiber size, internal nuclei, minor fatty replacement of muscle fibers, rimmed vacuoles or end stage myopathic changes (eg, major fatty replacement of muscle tissue) (72). In an American family with the S85C MATR3 mutation no changes compatible with a neurogenic process were observed on both muscle pathology and electromyography (78). Muscle biopsy showed numerous rimmed-vacuolated fibers with no neurogenic changes.…”

Section: Distal Myopathy and Matr3mentioning

confidence: 96%

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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Re-evaluation of the phenotype caused by the commonMATR3p.Ser85Cys mutation in a new family

Cited by 30 publications

References 12 publications

RETRACTED ARTICLE: Transgenic mice overexpressing the ALS-linked protein Matrin 3 develop a profound muscle phenotype

RETRACTED ARTICLE: Transgenic mice overexpressing the ALS-linked protein Matrin 3 develop a profound muscle phenotype

The unfolding spectrum of inherited distal myopathies

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

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