Myoglobinopathy is an adult-onset autosomal dominant myopathy with characteristic sarcoplasmic inclusions

Montse Olivé, Martin Engvall, Gianina Ravenscroft, Macarena Cabrera-Serrano, Hong Jiao, Carlo Augusto Bortolotti, Marcello Pignataro, Matteo Lambrughi, Haibo Jiang, Alistair R.R. Forrest, Núria Benseny-Cases, Stefan Hofbauer, Christian Obinger, Gianantonio Battistuzzi, Marzia Bellei, Marco Borsari, Giulia Di Rocco, Helena M. Viola, Livia C. Hool, Josep Cladera & 24 others Kristina Lagerstedt-Robinson, Fengqing Xiang, Anna Wredenberg, Francesc Miralles, Juan José Baiges, Edoardo Malfatti, Norma B. Romero, Nathalie Streichenberger, Christophe Vial, Kristl G. Claeys, Chiara S.M. Straathof, An Goris, Christoph Freyer, Martin Lammens, Guillaume Bassez, Juha Kere, Paula Clemente, Thomas Sejersen, Bjarne Udd, Noemí Vidal, Isidre Ferrer, Lars Edström, Anna Wedell, Nigel G. Laing

Research output: Contribution to journalArticle

Abstract

Myoglobin, encoded by MB, is a small cytoplasmic globular hemoprotein highly expressed in cardiac myocytes and oxidative skeletal myofibers. Myoglobin binds O 2, facilitates its intracellular transport and serves as a controller of nitric oxide and reactive oxygen species. Here, we identify a recurrent c.292C>T (p.His98Tyr) substitution in MB in fourteen members of six European families suffering from an autosomal dominant progressive myopathy with highly characteristic sarcoplasmic inclusions in skeletal and cardiac muscle. Myoglobinopathy manifests in adulthood with proximal and axial weakness that progresses to involve distal muscles and causes respiratory and cardiac failure. Biochemical characterization reveals that the mutant myoglobin has altered O 2 binding, exhibits a faster heme dissociation rate and has a lower reduction potential compared to wild-type myoglobin. Preliminary studies show that mutant myoglobin may result in elevated superoxide levels at the cellular level. These data define a recognizable muscle disease associated with MB mutation.

Original languageEnglish
Article number1396
JournalNature Communications
Volume10
Issue number1
DOIs
Publication statusPublished - 1 Dec 2019

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myoglobin
Myoglobin
Muscular Diseases
inclusions
muscles
Muscle
muscle cells
skeletal muscle
Muscles
inorganic peroxides
nitric oxide
mutations
Heme
Cardiac Myocytes
Superoxides
Respiratory Insufficiency
Reactive Oxygen Species
Myocardium
controllers
Nitric Oxide

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Olivé, Montse ; Engvall, Martin ; Ravenscroft, Gianina ; Cabrera-Serrano, Macarena ; Jiao, Hong ; Bortolotti, Carlo Augusto ; Pignataro, Marcello ; Lambrughi, Matteo ; Jiang, Haibo ; Forrest, Alistair R.R. ; Benseny-Cases, Núria ; Hofbauer, Stefan ; Obinger, Christian ; Battistuzzi, Gianantonio ; Bellei, Marzia ; Borsari, Marco ; Di Rocco, Giulia ; Viola, Helena M. ; Hool, Livia C. ; Cladera, Josep ; Lagerstedt-Robinson, Kristina ; Xiang, Fengqing ; Wredenberg, Anna ; Miralles, Francesc ; Baiges, Juan José ; Malfatti, Edoardo ; Romero, Norma B. ; Streichenberger, Nathalie ; Vial, Christophe ; Claeys, Kristl G. ; Straathof, Chiara S.M. ; Goris, An ; Freyer, Christoph ; Lammens, Martin ; Bassez, Guillaume ; Kere, Juha ; Clemente, Paula ; Sejersen, Thomas ; Udd, Bjarne ; Vidal, Noemí ; Ferrer, Isidre ; Edström, Lars ; Wedell, Anna ; Laing, Nigel G. / Myoglobinopathy is an adult-onset autosomal dominant myopathy with characteristic sarcoplasmic inclusions. In: Nature Communications. 2019 ; Vol. 10, No. 1.
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title = "Myoglobinopathy is an adult-onset autosomal dominant myopathy with characteristic sarcoplasmic inclusions",
abstract = "Myoglobin, encoded by MB, is a small cytoplasmic globular hemoprotein highly expressed in cardiac myocytes and oxidative skeletal myofibers. Myoglobin binds O 2, facilitates its intracellular transport and serves as a controller of nitric oxide and reactive oxygen species. Here, we identify a recurrent c.292C>T (p.His98Tyr) substitution in MB in fourteen members of six European families suffering from an autosomal dominant progressive myopathy with highly characteristic sarcoplasmic inclusions in skeletal and cardiac muscle. Myoglobinopathy manifests in adulthood with proximal and axial weakness that progresses to involve distal muscles and causes respiratory and cardiac failure. Biochemical characterization reveals that the mutant myoglobin has altered O 2 binding, exhibits a faster heme dissociation rate and has a lower reduction potential compared to wild-type myoglobin. Preliminary studies show that mutant myoglobin may result in elevated superoxide levels at the cellular level. These data define a recognizable muscle disease associated with MB mutation.",
author = "Montse Oliv{\'e} and Martin Engvall and Gianina Ravenscroft and Macarena Cabrera-Serrano and Hong Jiao and Bortolotti, {Carlo Augusto} and Marcello Pignataro and Matteo Lambrughi and Haibo Jiang and Forrest, {Alistair R.R.} and N{\'u}ria Benseny-Cases and Stefan Hofbauer and Christian Obinger and Gianantonio Battistuzzi and Marzia Bellei and Marco Borsari and {Di Rocco}, Giulia and Viola, {Helena M.} and Hool, {Livia C.} and Josep Cladera and Kristina Lagerstedt-Robinson and Fengqing Xiang and Anna Wredenberg and Francesc Miralles and Baiges, {Juan Jos{\'e}} and Edoardo Malfatti and Romero, {Norma B.} and Nathalie Streichenberger and Christophe Vial and Claeys, {Kristl G.} and Straathof, {Chiara S.M.} and An Goris and Christoph Freyer and Martin Lammens and Guillaume Bassez and Juha Kere and Paula Clemente and Thomas Sejersen and Bjarne Udd and Noem{\'i} Vidal and Isidre Ferrer and Lars Edstr{\"o}m and Anna Wedell and Laing, {Nigel G.}",
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Olivé, M, Engvall, M, Ravenscroft, G, Cabrera-Serrano, M, Jiao, H, Bortolotti, CA, Pignataro, M, Lambrughi, M, Jiang, H, Forrest, ARR, Benseny-Cases, N, Hofbauer, S, Obinger, C, Battistuzzi, G, Bellei, M, Borsari, M, Di Rocco, G, Viola, HM, Hool, LC, Cladera, J, Lagerstedt-Robinson, K, Xiang, F, Wredenberg, A, Miralles, F, Baiges, JJ, Malfatti, E, Romero, NB, Streichenberger, N, Vial, C, Claeys, KG, Straathof, CSM, Goris, A, Freyer, C, Lammens, M, Bassez, G, Kere, J, Clemente, P, Sejersen, T, Udd, B, Vidal, N, Ferrer, I, Edström, L, Wedell, A & Laing, NG 2019, 'Myoglobinopathy is an adult-onset autosomal dominant myopathy with characteristic sarcoplasmic inclusions' Nature Communications, vol. 10, no. 1, 1396. https://doi.org/10.1038/s41467-019-09111-2

Myoglobinopathy is an adult-onset autosomal dominant myopathy with characteristic sarcoplasmic inclusions. / Olivé, Montse; Engvall, Martin; Ravenscroft, Gianina; Cabrera-Serrano, Macarena; Jiao, Hong; Bortolotti, Carlo Augusto; Pignataro, Marcello; Lambrughi, Matteo; Jiang, Haibo; Forrest, Alistair R.R.; Benseny-Cases, Núria; Hofbauer, Stefan; Obinger, Christian; Battistuzzi, Gianantonio; Bellei, Marzia; Borsari, Marco; Di Rocco, Giulia; Viola, Helena M.; Hool, Livia C.; Cladera, Josep; Lagerstedt-Robinson, Kristina; Xiang, Fengqing; Wredenberg, Anna; Miralles, Francesc; Baiges, Juan José; Malfatti, Edoardo; Romero, Norma B.; Streichenberger, Nathalie; Vial, Christophe; Claeys, Kristl G.; Straathof, Chiara S.M.; Goris, An; Freyer, Christoph; Lammens, Martin; Bassez, Guillaume; Kere, Juha; Clemente, Paula; Sejersen, Thomas; Udd, Bjarne; Vidal, Noemí; Ferrer, Isidre; Edström, Lars; Wedell, Anna; Laing, Nigel G.

In: Nature Communications, Vol. 10, No. 1, 1396, 01.12.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Myoglobinopathy is an adult-onset autosomal dominant myopathy with characteristic sarcoplasmic inclusions

AU - Olivé, Montse

AU - Engvall, Martin

AU - Ravenscroft, Gianina

AU - Cabrera-Serrano, Macarena

AU - Jiao, Hong

AU - Bortolotti, Carlo Augusto

AU - Pignataro, Marcello

AU - Lambrughi, Matteo

AU - Jiang, Haibo

AU - Forrest, Alistair R.R.

AU - Benseny-Cases, Núria

AU - Hofbauer, Stefan

AU - Obinger, Christian

AU - Battistuzzi, Gianantonio

AU - Bellei, Marzia

AU - Borsari, Marco

AU - Di Rocco, Giulia

AU - Viola, Helena M.

AU - Hool, Livia C.

AU - Cladera, Josep

AU - Lagerstedt-Robinson, Kristina

AU - Xiang, Fengqing

AU - Wredenberg, Anna

AU - Miralles, Francesc

AU - Baiges, Juan José

AU - Malfatti, Edoardo

AU - Romero, Norma B.

AU - Streichenberger, Nathalie

AU - Vial, Christophe

AU - Claeys, Kristl G.

AU - Straathof, Chiara S.M.

AU - Goris, An

AU - Freyer, Christoph

AU - Lammens, Martin

AU - Bassez, Guillaume

AU - Kere, Juha

AU - Clemente, Paula

AU - Sejersen, Thomas

AU - Udd, Bjarne

AU - Vidal, Noemí

AU - Ferrer, Isidre

AU - Edström, Lars

AU - Wedell, Anna

AU - Laing, Nigel G.

PY - 2019/12/1

Y1 - 2019/12/1

N2 - Myoglobin, encoded by MB, is a small cytoplasmic globular hemoprotein highly expressed in cardiac myocytes and oxidative skeletal myofibers. Myoglobin binds O 2, facilitates its intracellular transport and serves as a controller of nitric oxide and reactive oxygen species. Here, we identify a recurrent c.292C>T (p.His98Tyr) substitution in MB in fourteen members of six European families suffering from an autosomal dominant progressive myopathy with highly characteristic sarcoplasmic inclusions in skeletal and cardiac muscle. Myoglobinopathy manifests in adulthood with proximal and axial weakness that progresses to involve distal muscles and causes respiratory and cardiac failure. Biochemical characterization reveals that the mutant myoglobin has altered O 2 binding, exhibits a faster heme dissociation rate and has a lower reduction potential compared to wild-type myoglobin. Preliminary studies show that mutant myoglobin may result in elevated superoxide levels at the cellular level. These data define a recognizable muscle disease associated with MB mutation.

AB - Myoglobin, encoded by MB, is a small cytoplasmic globular hemoprotein highly expressed in cardiac myocytes and oxidative skeletal myofibers. Myoglobin binds O 2, facilitates its intracellular transport and serves as a controller of nitric oxide and reactive oxygen species. Here, we identify a recurrent c.292C>T (p.His98Tyr) substitution in MB in fourteen members of six European families suffering from an autosomal dominant progressive myopathy with highly characteristic sarcoplasmic inclusions in skeletal and cardiac muscle. Myoglobinopathy manifests in adulthood with proximal and axial weakness that progresses to involve distal muscles and causes respiratory and cardiac failure. Biochemical characterization reveals that the mutant myoglobin has altered O 2 binding, exhibits a faster heme dissociation rate and has a lower reduction potential compared to wild-type myoglobin. Preliminary studies show that mutant myoglobin may result in elevated superoxide levels at the cellular level. These data define a recognizable muscle disease associated with MB mutation.

UR - http://www.scopus.com/inward/record.url?scp=85063585616&partnerID=8YFLogxK

U2 - 10.1038/s41467-019-09111-2

DO - 10.1038/s41467-019-09111-2

M3 - Article

VL - 10

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 1396

ER -