Nemaline myopathy

Genetic transmission in nemaline myopathy is the subject of some uncertainty. A Japanese study of 50 pedigrees came to the conclusion that autosomal dominant with reduced penetrance was the most probable mode. However a Finnish study presented evidence for autosomal recessive transmission. There is no evidence that severe and mild forms are genetically distinct and several pedigrees contain members showing widely differing clinical severity. A candidate gene for autosomal dominant nemaline myopathy has been localized to chromosome Iq 21—23. 

Figure 4. Nemaline myopathy electron micrograph shows nemaline rods (arrows) lying between disrupted myofibrils.

In severe neonatal nemaline myopathy virtually every muscle fiber shows multiple rods and all muscle fiber types are affected. However in juvenile cases, two different patterns of fiber type involvement are seen. In one there is a clear size difference between type 1 fibers, which are abnormally small (hypotrophic or atrophic) and which contain numerous nemaline rods, and type 2 fibers, which are either of normal diameter or hypertrophic and contain few, if any, nemaline rods. Other patients show a gross predominance of type 1 muscle fibers, again with rods virtually confined to this fiber type. These findings may be explicable in terms of the involvement of isoforms of a-actinin specific to slow and fast muscle fiber types. 

A hereditary disease common in Japan results from a defect in migration of neurons and is associated with brain malfonnation as well as muscular dystrophy. In nemaline myopathy a defect in nebulin leads to progressive weakness and often to death in infancy. 

One family with CCD arising from an RyRl mutation also had nemaline rods similar to those found with nemaline myopathies (NM) (Scacheri 2000). Muscle fibers from these patients show frequent clusters of rod-like structures. The autosomal dominant form of NM has been linked to mutations in the genes for a-tropomyosin and skeletal a-actin. A recessive form is associated with mutations in nebulin and a-tropomyosin. A major, unanswered question is whether and/or how a mutation in RyRl can produce a similar pathology. 

The most detailed Z-band structure to date has come from the extended Z-crystals found in muscles of patients with nemaline myopathy (Morris et al., 1990). This showed the unit cell of the structure to have the symmetry 432i2i in which the actin filaments themselves have 43 screw symmetry (i.e., they are on a left-handed 4/1 helix). In an earlier section the helical symmetry of typical actin filaments was described as a 13/6 helix of repeat 357.5 A. However, this is only one of a family of closely related symmetries. The actin filaments in insect flight muscle have 28/13 symmetry (28 actin subunits in 13 turns) and a repeat of 770 A. The normal 13/6 helix could also be called a 26/12 helix (with a repeat of 715 A), which shows the similarity between the two structures one is a slightly unwound version of the other. One of the features of the 28/13 helix is that 28 is divisible by 4, which means that, starting from a given actin monomer, there must be three other monomers with exactly 90° azimuthal... 

Wallgren-Petterson, C., and Laing, N. G. (2003). 109th ENMC International Workshop 5th Workshop on nemaline myopathy, 11-13 October 2002, Naarden, The Netherlands. Neuromuscular Disorders 13, 501-507. 

Ilkovski, B., Cooper, S. T., Nowak, K., Ryan, M. M., Yang, N., Schnell, C., et al. (2001) Nemaline myopathy caused by mutations in the muscle alpha-skeletal-actin gene. Am J Hum Genet 68, 1333-1343. 

Autosomal dominant 15ql4 Actin Actin Nemaline myopathy... 

Resistance to suxamethonium has been seen in von Recklinghausen s disease (4) and nemaline myopathy (5). 

Heard SO, Kaplan RF. Neuromuscular blockade in a patient with nemaline myopathy. Anesthesiology 1983 59(6) 588-90. 

Two rare diseases, central core disease (S6) and nemaline myopathy (S7) are said, from microscopic evidence, to affect the myofibrils, but little work has been done on the biochemistry of these conditions. 

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