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

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

OBJECTIVE: To investigate single muscle fiber contractile performance in muscle biopsies from patients with facioscapulohumeral muscular dystrophy (FSHD), one of the most common hereditary muscle disorders.

METHODS: We 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.

RESULTS: Single 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.

CONCLUSION: Muscle 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
JournalNeurology
DOIs
Publication statusE-pub ahead of print - 21 Jan 2020

Cite this

Lassche, S., Voermans, N. C., van der Pijl, R., van den Berg, M., Heerschap, A., van Hees, H., ... van Engelen, B. G. M. (2020). Preserved single muscle fiber specific force in facioscapulohumeral muscular dystrophy. Neurology. https://doi.org/10.1212/WNL.0000000000008977
Lassche, Saskia ; Voermans, Nicol C ; van der Pijl, Robbert ; van den Berg, Marloes ; Heerschap, Arend ; van Hees, Hieronymus ; Kusters, Benno ; van der Maarel, Silvère M ; Ottenheijm, Coen A C ; van Engelen, Baziel G M. / Preserved single muscle fiber specific force in facioscapulohumeral muscular dystrophy. In: Neurology. 2020.
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title = "Preserved single muscle fiber specific force in facioscapulohumeral muscular dystrophy",
abstract = "OBJECTIVE: To investigate single muscle fiber contractile performance in muscle biopsies from patients with facioscapulohumeral muscular dystrophy (FSHD), one of the most common hereditary muscle disorders.METHODS: We 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.RESULTS: Single 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.CONCLUSION: Muscle 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.",
author = "Saskia Lassche and Voermans, {Nicol C} and {van der Pijl}, Robbert and {van den Berg}, Marloes and Arend Heerschap and {van Hees}, Hieronymus and Benno Kusters and {van der Maarel}, {Silv{\`e}re M} and Ottenheijm, {Coen A C} and {van Engelen}, {Baziel G M}",
note = "{\circledC} 2020 American Academy of Neurology.",
year = "2020",
month = "1",
day = "21",
doi = "10.1212/WNL.0000000000008977",
language = "English",
journal = "Neurology",
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Lassche, S, Voermans, NC, van der Pijl, R, van den Berg, M, Heerschap, A, van Hees, H, Kusters, B, van der Maarel, SM, Ottenheijm, CAC & van Engelen, BGM 2020, 'Preserved single muscle fiber specific force in facioscapulohumeral muscular dystrophy' Neurology. https://doi.org/10.1212/WNL.0000000000008977

Preserved single muscle fiber specific force in facioscapulohumeral muscular dystrophy. / Lassche, Saskia; Voermans, Nicol C; van der Pijl, Robbert; van den Berg, Marloes; Heerschap, Arend; van Hees, Hieronymus; Kusters, Benno; van der Maarel, Silvère M; Ottenheijm, Coen A C; van Engelen, Baziel G M.

In: Neurology, 21.01.2020.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Preserved single muscle fiber specific force in facioscapulohumeral muscular dystrophy

AU - Lassche, Saskia

AU - Voermans, Nicol C

AU - van der Pijl, Robbert

AU - van den Berg, Marloes

AU - Heerschap, Arend

AU - van Hees, Hieronymus

AU - Kusters, Benno

AU - van der Maarel, Silvère M

AU - Ottenheijm, Coen A C

AU - van Engelen, Baziel G M

N1 - © 2020 American Academy of Neurology.

PY - 2020/1/21

Y1 - 2020/1/21

N2 - OBJECTIVE: To investigate single muscle fiber contractile performance in muscle biopsies from patients with facioscapulohumeral muscular dystrophy (FSHD), one of the most common hereditary muscle disorders.METHODS: We 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.RESULTS: Single 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.CONCLUSION: Muscle 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.

AB - OBJECTIVE: To investigate single muscle fiber contractile performance in muscle biopsies from patients with facioscapulohumeral muscular dystrophy (FSHD), one of the most common hereditary muscle disorders.METHODS: We 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.RESULTS: Single 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.CONCLUSION: Muscle 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.

U2 - 10.1212/WNL.0000000000008977

DO - 10.1212/WNL.0000000000008977

M3 - Article

JO - Neurology

JF - Neurology

SN - 0028-3878

ER -

Lassche S, Voermans NC, van der Pijl R, van den Berg M, Heerschap A, van Hees H et al. Preserved single muscle fiber specific force in facioscapulohumeral muscular dystrophy. Neurology. 2020 Jan 21. https://doi.org/10.1212/WNL.0000000000008977