The Spectrum of Rod Myopathies

Heffernan, L. P.; Rewcastle, N. B.; Humphrey, J. A. C.

doi:10.1001/archneur.1968.00470350087008

Cited by 36 publications

(5 citation statements)

References 9 publications

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“…Abundant nemaline rods and occasional leakage of Z-disks were revealed. The nemaline rods conformed to the observations made by Engel (1967), Heffernan et al (1968), Karpati et al (1971), etc. The rods showed a rectangular lattice structure with transverse and longitudinal periodicities of 165 -185 ~ and 130 -140 A.…”

Section: Electron Microscopical Studysupporting

confidence: 88%

Nemaline myopathy: Histological, histochemical and ultrastructural studies

et al. 1978

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Histological, histochemical and ultrastructural studies were performed on muscle biopsies from three siblings with congenital nemaline myopathy. Histological studies revealed type I fibre atrophy and type II fibre paucity. Ultrastructural studies of intramuscular nerves showed that the axonal diameters were very narrow compared with the width of myelin lamellae. Granular or membranous osmiophilic material occurred in the adaxonal Schwann cell cytoplasm and had a periodicity of 33--38 A. The neuromuscular junctions showed degenerative features such as glycogen granules or myelin figures in 27.1% of total terminal axons. The secondary synaptic clefts were markedly decreased in number and short in length. Myotendinous junction-like structures were found in 5.5% of the muscle fibres near the neuromuscular junctions, and often near sites of fibre-splitting. Rods in nemaline myopathy might be caused as a result of longitudinal splitting and disruption of fibres due to deficient regeneration of the muscle fibres associated with neurotrophic abnormalities.

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Section: Electron Microscopical Studysupporting

confidence: 88%

Nemaline myopathy: Histological, histochemical and ultrastructural studies

et al. 1978

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“…Cfl2 mouse studies report no obvious NMJ defects; it is possible that a subtle change on the postsynaptic membrane would not be appreciated when only visualizing the motor neuron and acetylcholine receptors (Agrawal et al, 2012; Gurniak et al, 2014). Nevertheless, some reports from human NM patient biopsies imaged by TEM report alterations at the postsynapse, including collapsed or dilated primary and secondary synaptic clefts (Fukuhara et al, 1978; Heffernan et al, 1968; Karpati et al, 1971). We see a collapse of the synaptic cleft via TEM in the DmCFL KD model.…”

Section: Discussionmentioning

confidence: 99%

“…To further investigate the DmCFL KD model, we conducted RNA sequencing which identified changes in genes related to the neuromuscular junction (NMJ), the specialized synapse where the presynaptic motor neuron and postsynaptic muscle communicate. Early case reports examining NM muscle biopsies provide evidence of NMJ disruption, describing abnormal motor end plates and synaptic clefts (Fukuhara et al, 1978; Heffernan et al, 1968). Moreover, electromyography shows a myopathic pattern in NM patients, although it is unclear if there is additional superimposed NMJ transmission defect.…”

Section: Introductionmentioning

confidence: 99%

Muscle cofilin alters neuromuscular junction postsynaptic development to strengthen functional neurotransmission

Christophers,

Leahy,

Soffar

et al. 2023

Preprint

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Cofilin, an actin severing protein, plays critical roles in muscle sarcomere addition and maintenance. Our previous work has shownDrosophilacofilin (DmCFL) knockdown causes progressive deterioration of muscle structure and function and produces features seen in nemaline myopathy (NM) caused by cofilin mutations. We hypothesized that disruption of actin cytoskeleton dynamics byDmCFLknockdown would impact other aspects of muscle development, and, thus, conducted an RNA sequencing analysis which unexpectedly revealed upregulated expression of numerous neuromuscular junction (NMJ) genes. We found that DmCFL is enriched in the muscle postsynaptic compartment and that DmCFL deficiency causes F-actin disorganization in this subcellular domain prior to the sarcomere defects observed later in development. Despite NMJ gene expression changes, we found no significant changes in gross presynaptic Bruchpilot active zones or total postsynaptic glutamate receptor levels. However,DmCFLknockdown results in mislocalization of glutamate receptors containing the GluRIIA subunit in more deteriorated muscles and neurotransmission strength is strongly impaired. These findings expand our understanding of cofilin’s roles in muscle to include NMJ structural development and suggest that NMJ defects may contribute to NM pathophysiology.Summary statementCofilin regulates muscle postsynaptic actin organization, structural maintenance, glutamate receptor composition, and neuromuscular junction function in aDrosophilanemaline myopathy disease model.

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“…The X-Iinked neonatal form is represented by 2 male brothers who presented after birth with severe generalized weakness complicated by ir reversible respiratory failure and death. A 25-year-old previously healthy male with moderate proximal weak ness represents the third group, developing a benign or a fulminant myopathy during adulthood [5].…”

Section: Discussionmentioning

confidence: 99%

“…Subsequent reports address a wider heterogeneity documenting neonates with NM who died of fulminant respiratory failure [3,4] and newly diagnosed adults presenting with weakness [5], The clinical and laborato ry features of 13 patients with NM are reported herein. To add to the clinical spectrum of NM previously report ed, we also describe 2 infants with initial moderate weakness who subsequently developed irreversible respiratory failure which was successfully treated with long-term ventilatory support.…”

Section: Introductionmentioning

confidence: 97%

Heterogeneity of Nemaline Myopathy

1988

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The marked heterogeneity of nemaline myopathy is again shown in the present series of 13 patients. Most children have a long-standing, mild, and slowly progressing proximal myopathy. Two brothers with extreme weakness died during the neonatal period of respiratory failure representing the X-linked variant. One adult with proximal weakness was also diagnosed as having nemaline myopathy. An unusual course was observed in 2 infants who initially had moderate weakness but subsequently developed severe generalized weakness including respiratory muscles. This led to irreversible respiratory failure requiring continuous ventilatory support for as long as 9 and 15 years, respectively. Although uncommon, the possibility of an imminent respiratory failure in initially weak infants should also be taken into account within the clinical spectrum of nemaline myopathy.

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The Spectrum of Rod Myopathies

Cited by 36 publications

References 9 publications

Nemaline myopathy: Histological, histochemical and ultrastructural studies

Nemaline myopathy: Histological, histochemical and ultrastructural studies

Muscle cofilin alters neuromuscular junction postsynaptic development to strengthen functional neurotransmission

Heterogeneity of Nemaline Myopathy

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