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. 2015;2(3):291-299.
doi: 10.3233/JND-150077.

Immunohistochemical Characterization of Facioscapulohumeral Muscular Dystrophy Muscle Biopsies

Jeffrey M Statland  1 , Karen J Odrzywolski  2 , Bharati Shah  2 , Don Henderson  2 , Alex F Fricke  3 , Silvère M van der Maarel  4 , Stephen J Tapscott  5 , Rabi Tawil  2
Affiliations

Immunohistochemical Characterization of Facioscapulohumeral Muscular Dystrophy Muscle Biopsies

Jeffrey M Statland et al. J Neuromuscul Dis. 2015.

Abstract

Background: Posited pathological mechanisms in Facioscapulohumeral Muscular Dystrophy (FSHD) include activation in somatic tissue of normally silenced genes, increased susceptibility to oxidative stress, and induction of apoptosis.

Objective: To determine the histopathological changes in FSHD muscle biopsies and compare to possible pathological mechanisms of disease.

Methods: We performed a cross-sectional study on quadriceps muscle biopsies from 32 genetically confirmed FSHD participants, compared to healthy volunteers and myotonic dystrophy type 1 as disease controls. Biopsies were divided into groups to evaluate apoptosis rates, capillary density, myonuclear and satellite cell counts.

Results: Apoptosis rates were increased in FSHD (n=10, 0.74%) compared to myotonic dystrophy type 1 (n=10, 0.14%, P=0.003) and healthy volunteers (n=14, 0.13%, P=0.002). Apoptosis was higher in FSHD patients with the smallest residual D4Z4 fragments. Capillary density was decreased in FSHD1 (n=10, 316 capillaries/mm2) compared to healthy volunteers (n=15, 448 capillaries/mm2, P=0.001). No differences were seen in myonuclear or satellite cell counts.

Conclusions: Preliminary evidence for increased apoptosis rates and reduced capillary density may reflect histopathological correlates of disease activity in FSHD. The molecular-pathological correlates to these changes warrants further investigation.

Keywords: Facioscapulohumeral muscular dystrophy; apoptosis rates; capillary density; myonuclear density; satellite cell counts.

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Figures

Fig.1
Fig.1
Apoptosis. A) DAPI stains nuclei blue. B) TUNEL stained degenerating nuclei green. C) Overlay stained with DAPI and TUNEL shows degenerating myonuclei. Laminin alpha-2 shows outline of myofiber in red. DAPI = 4,6-diamidino-2-phenylindole; TUNEL = terminal deoxynucleotidyl transferase dUTP nick end labeling.
Fig.2
Fig.2
Relationships of histopathology findings. A) Relationship of apoptosis rate to genetic mutation (≤18kb [n = 3]; 19–27 kb [n = 4];and >27 kb [n = 3]); B) Relationship of apoptosis rate to age adjusted clinical severity score; and C) Relationship of capillary density measurement to the fiber type ratio.
See this image and copyright information in PMC

References

    1. Flanigan K.M., Coffeen C.M., Sexton L., Stauffer D., Brunner S., Leppert M.F. Genetic characterization of a large,historically significant Utah kindred with facioscapulohumeraldystrophy. Neuromuscul Disord. 2001;11:525–529. - PubMed
    1. Padberg G.W., Frants R.R., Brouwer O.F., Wijmenga C., Bakker E., Sandkuijl L.A. Facioscapulohumeral muscular dystrophy in the Dutch population. Muscle Nerve. 1995;2:S81–S84. - PubMed
    1. Lemmers R.J., Tawil R., Petek L.M., et al. Digenic inheritance of an SMCHD1 mutation and an FSHD-permissive D4Z4 allele causes facioscapulohumeral muscular dystrophy type 2. Nat Genet. 2012;44:1370–1374. - PMC - PubMed
    1. Lemmers R.J., van der Vliet P.J., Klooster R., et al. A unifying genetic model for facioscapulohumeral muscular dystrophy. Science. 2010;329:1650–1653. - PMC - PubMed
    1. Celegato B., Capitanio D., Pescatori M., et al. Parallel protein and transcript profiles of FSHD patient muscles correlate to the D4Z4 arrangement and reveal a common impairment of slow to fast fibre differentiation and a general deregulation of MyoD-dependent genes. Proteomics. 2006;6:5303–5321. - PubMed

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