Preserved single muscle fiber specific force in facioscapulohumeral muscular dystrophy

Saskia Lassche*, Nicol C. Voermans, Robbert van der Pijl, Marloes van den Berg, Arend Heerschap, Hieronymus van Hees, Benno Kusters, Silvère M. van der Maarel, Coen A. C. Ottenheijm, Baziel G. M. van Engelen

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

ObjectiveTo investigate single muscle fiber contractile performance in muscle biopsies from patients with facioscapulohumeral muscular dystrophy (FSHD), one of the most common hereditary muscle disorders.MethodsWe collected 50 muscle biopsies (26 vastus lateralis, 24 tibialis anterior) from 14 patients with genetically confirmed FSHD and 12 healthy controls. Single muscle fibers (n = 547) were isolated for contractile measurements. Titin content and titin phosphorylation were examined in vastus lateralis muscle biopsies.ResultsSingle muscle fiber specific force was intact at saturating and physiologic calcium concentrations in all FSHD biopsies, with (FSHDFAT) and without (FSHDNORMAL) fatty infiltration, compared to healthy controls. Myofilament calcium sensitivity of force is increased in single muscle fibers obtained from FSHD muscle biopsies with increased fatty infiltration, but not in FSHD muscle biopsies without fatty infiltration (pCa50: 5.77-5.80 in healthy controls, 5.74-5.83 in FSHDNORMAL, and 5.86-5.90 in FSHDFAT single muscle fibers). Cross-bridge cycling kinetics at saturating calcium concentrations and myofilament cooperativity did not differ from healthy controls. Development of single muscle fiber passive tension was changed in all FSHD vastus lateralis and in FSHDFAT tibialis anterior, resulting in increased fiber stiffness. Titin content was increased in FSHD vastus lateralis biopsies; however, titin phosphorylation did not differ from healthy controls.ConclusionMuscle weakness in patients with FSHD is not caused by reduced specific force of individual muscle fibers, even in severely affected tissue with marked fatty infiltration of muscle tissue.
Original languageEnglish
Pages (from-to)e1157-e1170
JournalNeurology
Volume94
Issue number11
Early online date21 Jan 2020
DOIs
Publication statusPublished - 17 Mar 2020

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