Clinical History:
Both of these patients were identified to have mutations in the FNLC gene, albeit in regions that affect different domains of the encoded protein. Pathologic variants in the FLNC gene are associated with myofibrillar myopathy (MFM) and/or distal myopathy clinicopathologic phenotypes.
Pathologic variants involving different protein domains may show different clinical and pathologic features.
A. True
B. False
Answer:
True
These cases nicely demonstrate that the pathologic changes of different genetic variants (mutations) may differ. This makes sense, given that different parts of a protein may have different biologic functions.
The first case shows muscle fiber size variation with frequent ring fibers and lobulated muscle fibers. The second case demonstrates areas of myofibrillar disorganization with congophilia, and some autophagic vacuolar change that are characteristic features of myofibrillar myopathy that may be caused by pathogenic variants in multiple genes.
Reference(s) / Additional Reading:
- Savarese M, Sarparanta J, Vihola A, et al. Panorama of the distal myopathies. Acta Myol. 2020;39(4):245-265. Published 2020 Dec 1.
- Selcen D. Myofibrillar myopathies. Neuromuscul Disord. 2011;21(3):161-171. doi:10.1016/j.nmd.2010.12.007oi:10.36185/2532-1900-028
- Duff RM, Tay V, Hackman P, et al. Mutations in the N-terminal actin-binding domain of filamin C cause a distal myopathy. Am J Hum Genet. 2011;88(6):729-740. doi:10.1016/j.ajhg.2011.04.021
- Mao Z, Nakamura F. Structure and Function of Filamin C in the Muscle Z-Disc. Int J Mol Sci. 2020;21(8):2696. Published 2020 Apr 13. doi:10.3390/ijms21082696
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