14.6.1 POJA-L6241+6181+6182+6183 Nemaline myopathy I (human)
14.6.1 POJA-L6241+6181+6182+6183 Nemaline myopathy I (human)
(A, B. Light micrographs by courtesy of H. ter Laak PhD Section Neuropathology, retired staff member Department of Pathology, Radboud university medical center, Nijmegen, The Netherland)
(C, D. Electron micrographs by courtesy of L. Eshuis BSc Section Electron microscopy, Department of Pathology, Radboud university medical center, Nijmegen, The Netherlands)
Title: Nemaline myopathy I (human)
Description:
(A): Trichrome staining showing accumulation of nemaline bodies in atrophic fibres, rod-shaped components that are diagnostic for the condition called nemaline rod myopathy. The most common genetic form of Nemaline Myopathy is caused by a mutation in the nebulin gene and resulting in progressive muscle weakness. It is an accumulation of non-functional nebulin molecules in rod shaped granules.
(B): Semi-thin section of muscle fibres, stained with toluidine blue, showing muscle fibres full of nemaline bodies subsarcolemmally.
(C+D): Electron micrographs of the nemaline rod shaped bodies accumulated at the periphery of a muscle fibre and in between of the impaired myosin and actin filaments, causing disorganisation in the muscle fibres.
Introduction: Nemaline myopathy (NM) is a congenital myopathy that primarily affects skeletal muscles and is clinically characterised by muscle weakness, hypotonia and depressed or absent deep tendon reflexes.
Aetiology: Mutations in the nebulin and actin filaments genes are most frequently involved. These genes are involved in the production of proteins in the sarcomeres of skeletal muscles. Mutations in any of these genes lead to disorganisation of the sarcomeric proteins of skeletal muscles resulting in an abnormal interaction of these proteins and disruption of muscle contraction. Inefficient muscle contraction leads to muscle weakness and the other features of nemaline myopathy.
Epidemiology: NM is a disease caused by mutation of at least 13 known genes. The most frequent genetic cause of autosomal recessive NM are mutations in the nebulin gene (NEB), whereas heterozygous pathogenic variants in the alpha-skeletal actin gene (ACTA1) are the most prevalent cause of autosomal dominant NM.
Pathophysiology: Formations of rods or so-called nemaline bodies represent a common pathophysiogical response of the skeletal muscle. The nemaline bodies are largely made up of a-actinin, in conjunction with other filaments such as actin and nebulin. Rods are also found in other neuromuscular diseases and unrelated mitochondrial myopathies.
Histopathology: Microscopically these muscle fibres appear abnormal and contain rod-like structures called nemaline bodies, visual as red thread-like material in Gomori trichrome stained tissue sections and as electron dense deposits in electron microscopy. The distribution of rods may be random in the muscle cells but tend to localise as clusters near the (sub)-sarcolemma or around the nuclei. Congenital myopathies: an update. Claeys K. 2019 https://onlinelibrary.wiley.com/doi/full/10.1111/dmcn.14365
See also
Keywords/Mesh: locomotor system, skeletal muscle, striated muscle, neuromuscular disease, congenital myopathy, nemaline myopathy, rod body myopathy, nemaline body, rod, Z-line, a -actinin, electron microscopy, pathology, POJA collection
(C, D. Electron micrographs by courtesy of L. Eshuis BSc Section Electron microscopy, Department of Pathology, Radboud university medical center, Nijmegen, The Netherlands)
Title: Nemaline myopathy I (human)
Description:
(A): Trichrome staining showing accumulation of nemaline bodies in atrophic fibres, rod-shaped components that are diagnostic for the condition called nemaline rod myopathy. The most common genetic form of Nemaline Myopathy is caused by a mutation in the nebulin gene and resulting in progressive muscle weakness. It is an accumulation of non-functional nebulin molecules in rod shaped granules.
(B): Semi-thin section of muscle fibres, stained with toluidine blue, showing muscle fibres full of nemaline bodies subsarcolemmally.
(C+D): Electron micrographs of the nemaline rod shaped bodies accumulated at the periphery of a muscle fibre and in between of the impaired myosin and actin filaments, causing disorganisation in the muscle fibres.
Introduction: Nemaline myopathy (NM) is a congenital myopathy that primarily affects skeletal muscles and is clinically characterised by muscle weakness, hypotonia and depressed or absent deep tendon reflexes.
Aetiology: Mutations in the nebulin and actin filaments genes are most frequently involved. These genes are involved in the production of proteins in the sarcomeres of skeletal muscles. Mutations in any of these genes lead to disorganisation of the sarcomeric proteins of skeletal muscles resulting in an abnormal interaction of these proteins and disruption of muscle contraction. Inefficient muscle contraction leads to muscle weakness and the other features of nemaline myopathy.
Epidemiology: NM is a disease caused by mutation of at least 13 known genes. The most frequent genetic cause of autosomal recessive NM are mutations in the nebulin gene (NEB), whereas heterozygous pathogenic variants in the alpha-skeletal actin gene (ACTA1) are the most prevalent cause of autosomal dominant NM.
Pathophysiology: Formations of rods or so-called nemaline bodies represent a common pathophysiogical response of the skeletal muscle. The nemaline bodies are largely made up of a-actinin, in conjunction with other filaments such as actin and nebulin. Rods are also found in other neuromuscular diseases and unrelated mitochondrial myopathies.
Histopathology: Microscopically these muscle fibres appear abnormal and contain rod-like structures called nemaline bodies, visual as red thread-like material in Gomori trichrome stained tissue sections and as electron dense deposits in electron microscopy. The distribution of rods may be random in the muscle cells but tend to localise as clusters near the (sub)-sarcolemma or around the nuclei. Congenital myopathies: an update. Claeys K. 2019 https://onlinelibrary.wiley.com/doi/full/10.1111/dmcn.14365
See also
- 14.6.1 POJA-L6323+6182 Nemaline myopathy II
Keywords/Mesh: locomotor system, skeletal muscle, striated muscle, neuromuscular disease, congenital myopathy, nemaline myopathy, rod body myopathy, nemaline body, rod, Z-line, a -actinin, electron microscopy, pathology, POJA collection