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. 2020 Aug;140(2):231-235.
doi: 10.1007/s00401-020-02164-4. Epub 2020 May 25.

Multiomic elucidation of a coding 99-mer repeat-expansion skeletal muscle disease

Alessandra Ruggieri  1   2 , Sergey Naumenko  3 , Martin A Smith  4   5   6   7 , Eliana Iannibelli  1 , Flavia Blasevich  1 , Cinzia Bragato  1   8 , Sara Gibertini  1 , Kirston Barton  7 , Matthias Vorgerd  9 , Katrin Marcus  10 , Peixiang Wang  11 , Lorenzo Maggi  1 , Renato Mantegazza  1 , James J Dowling  11 , Rudolf A Kley  9   12 , Marina Mora  1 , Berge A Minassian  13   14
Affiliations

Multiomic elucidation of a coding 99-mer repeat-expansion skeletal muscle disease

Alessandra Ruggieri et al. Acta Neuropathol. 2020 Aug.
No abstract available

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Figures

Fig. 1
Fig. 1
Pedigree and muscle histopathology. a Pedigree. b Gomori trichrome and H&E staining, respectively, in patients IV:3 and V:3, showing vacuoles (arrows) rimmed, empty, or containing granular or basophilic material (arrowheads) mainly located in the subsarcolemmal region of fibers, fiber size variability, central nuclei and mildly increased endomysial spaces. Note minimal changes in V:13. c Electron micrographs unveiling (upper panel) granular debris within a small subsarcolemmal vacuole (arrow) opening to the fiber’s surface and sarcolemmal interruption (arrowheads); (lower panel) vacuoles located in the subsarcolemmal region or deep in the sarcoplasm, containing small vesicles, membranous bodies and granular debris. d Confocal microscopy of p62/SQSTM1 and FK2 immunostaining showing positivity and almost complete overlap of both proteins in vacuoles and subsarcolemmae of affected fibers, more numerous with increasing clinical severity
Fig. 2
Fig. 2
Perilipin-4 expression and aggrephagy. a Exon 3 PCR amplification showing besides the wild-type band, a second one approximately 1000 bp higher only in affected family members. b Perilipin-4 western blot revealing a second band in patient muscle, absent in controls. c Immunohistochemistry showing perilipin-4 within vacuoles and in the subsarcolemmal region in all affected fibers, overlapping with FK2 by confocal microscopy analysis. d, e Co-localization of perilipin-4 and aggrephagy-related proteins NBR1 (d) and WDFY3 (e), showing upregulation of both in patient muscle, with good overlap of NBR1-perilipin-4and increase of WDFY3 near perilipin-4
See this image and copyright information in PMC

References

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