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GENATLAS PHENOTYPE
last update : 09-05-2018
Symbol NEM4
Location 9p13.3
Name nemaline myopathy 4
Other name(s) Cap myopathy
Corresponding gene TPM2
Main clinical features
  • difficulty in walking, facial and neck flexor weakness in infancy, arthrogryposis, multiple pterygia, feeding difficulties and severe hypotonia with high-arched palate, narrow face, elongated funnel chest, lordosis, and kyphoscoliosis from birth
  • predominant involvement of masticatory and distal leg muscles with the other regions relatively spared (PMID: 22980765))
  • at muscle biopsy type 1 fiber predominance consistent with nemaline myopathy, but nemaline rods can vary substantially
  • electron microscopy showed abnormally arranged myofibrils with an abnormal sarcomere pattern and irregular or streaming Z lines
    • Genetic determination autosomal dominant
    Function/system disorder neuromuscular
    Type disease
    Remark(s)
  • mutations can alter the expression of other sarcomeric TM isoforms and that the perturbation of TM isoform levels may affect the dimer preference within the thin filaments, which may contribute to muscle weakness as a result of both functional and structural changes in muscle (Nilsson 2008)
  • during activation, the single AA change in the protein partially inhibits both calcium- and myosin-induced tropomyosin movement over the thin filament, preventing actin conformational changes and thereby reducing the number of cross-bridges and the consequent force production (Ochala 2010)
  • specifically, the TPM2-null mutations decreased cooperative thin filament activation with simultaneous reductions in myosin cross-bridge number and force production, but TPM2-E181K mutation increased thin filament activation, cross-bridge binding and force generation (PMID: 22798622))