Josine M. de Winter
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View article: Pathogenic <i>TNNI1</i> variants disrupt sarcomere contractility resulting in hypo- and hypercontractile muscle disease
Pathogenic <i>TNNI1</i> variants disrupt sarcomere contractility resulting in hypo- and hypercontractile muscle disease Open
Troponin I (TnI) regulates thin filament activation and muscle contraction. Two isoforms, TnI-fast ( TNNI2 ) and TnI-slow ( TNNI1 ), are predominantly expressed in fast- and slow-twitch myofibers, respectively. TNNI2 variants are a rare ca…
View article: <i>Tirasemtiv</i> enhances submaximal muscle tension in an <i>Acta1</i>:p.Asp286Gly mouse model of nemaline myopathy
<i>Tirasemtiv</i> enhances submaximal muscle tension in an <i>Acta1</i>:p.Asp286Gly mouse model of nemaline myopathy Open
Nemaline myopathies are the most common form of congenital myopathies. Variants in ACTA1 (NEM3) comprise 15–25% of all nemaline myopathy cases. Patients harboring variants in ACTA1 present with a heterogeneous disease course characterized …
View article: KBTBD13 is an actin-binding protein that modulates muscle kinetics
KBTBD13 is an actin-binding protein that modulates muscle kinetics Open
View article: Small molecule drugs to improve sarcomere function in those with acquired and inherited myopathies
Small molecule drugs to improve sarcomere function in those with acquired and inherited myopathies Open
During the past decade, several small molecule drugs that improve the contractility of skeletal muscle fibers have been developed. In this review, we provide an overview of the available literature and the mechanisms of action of small mol…
View article: <i>KBTBD13</i> is a novel cardiomyopathy gene
<i>KBTBD13</i> is a novel cardiomyopathy gene Open
KBTBD13 variants cause nemaline myopathy type 6 (NEM6). The majority of NEM6 patients harbors the Dutch founder variant, c.1222C>T, p.Arg408Cys (KBTBD13 p.R408C). Although KBTBD13 is expressed in cardiac muscle, cardiac involvement in NEM6…
View article: Troponin Variants in Congenital Myopathies: How They Affect Skeletal Muscle Mechanics
Troponin Variants in Congenital Myopathies: How They Affect Skeletal Muscle Mechanics Open
The troponin complex is a key regulator of muscle contraction. Multiple variants in skeletal troponin encoding genes result in congenital myopathies. TNNC2 has been implicated in a novel congenital myopathy, TNNI2 and TNNT3 in distal arthr…
View article: Acute and chronic <i>tirasemtiv</i> treatment improves <i>in vivo</i> and <i>in vitro</i> muscle performance in actin-based nemaline myopathy mice
Acute and chronic <i>tirasemtiv</i> treatment improves <i>in vivo</i> and <i>in vitro</i> muscle performance in actin-based nemaline myopathy mice Open
Nemaline myopathy, a disease of the actin-based thin filament, is one of the most frequent congenital myopathies. To date, no specific therapy is available to treat muscle weakness in nemaline myopathy. We tested the ability of tirasemtiv,…
View article: Pathogenic variants in TNNC2 cause congenital myopathy due to an impaired force response to calcium
Pathogenic variants in TNNC2 cause congenital myopathy due to an impaired force response to calcium Open
Troponin C (TnC) is a critical regulator of skeletal muscle contraction; it binds Ca2+ to activate muscle contraction. Surprisingly, the gene encoding fast skeletal TnC (TNNC2) has not yet been implicated in muscle disease. Here, we report…
View article: NEM6, KBTBD13-Related Congenital Myopathy: Myopathological Analysis in 18 Dutch Patients Reveals Ring Rods Fibers, Cores, Nuclear Clumps, and Granulo-Filamentous Protein Material
NEM6, KBTBD13-Related Congenital Myopathy: Myopathological Analysis in 18 Dutch Patients Reveals Ring Rods Fibers, Cores, Nuclear Clumps, and Granulo-Filamentous Protein Material Open
Nemaline myopathy type 6 (NEM6), KBTBD13-related congenital myopathy is caused by mutated KBTBD13 protein that interacts improperly with thin filaments/actin, provoking impaired muscle-relaxation kinetics. We describe muscle morphology in …
View article: KBTBD13 is an actin-binding protein that modulates muscle kinetics
KBTBD13 is an actin-binding protein that modulates muscle kinetics Open
The mechanisms that modulate the kinetics of muscle relaxation are critically important for muscle function. A prime example of the impact of impaired relaxation kinetics is nemaline myopathy caused by mutations in KBTBD13 (NEM6). In addit…
View article: Recessive MYH7-related myopathy in two families
Recessive MYH7-related myopathy in two families Open
View article: Sarcomere Dysfunction in Nemaline Myopathy
Sarcomere Dysfunction in Nemaline Myopathy Open
Nemaline myopathy (NM) is among the most common non-dystrophic congenital myopathies (incidence 1:50.000). Hallmark features of NM are skeletal muscle weakness and the presence of nemaline bodies in the muscle fiber. The clinical phenotype…
View article: <i>A two-faced cysteine residue modulates skeletal muscle contraction</i>. Focus on “<i>S</i>-nitrosylation and <i>S</i>-glutathionylation of Cys134 on troponin I have opposing competitive actions on Ca<sup>2+</sup> sensitivity in rat fast-twitch muscle fibers
<i>A two-faced cysteine residue modulates skeletal muscle contraction</i>. Focus on “<i>S</i>-nitrosylation and <i>S</i>-glutathionylation of Cys134 on troponin I have opposing competitive actions on Ca<sup>2+</sup> sensitivity in rat fast-twitch muscle fibers Open
View article: Nemaline myopathy: pathophysiology and therapeutic targets
Nemaline myopathy: pathophysiology and therapeutic targets Open
View article: Muscle weakness in respiratory and peripheral skeletal muscles in a mouse model for nebulin-based nemaline myopathy
Muscle weakness in respiratory and peripheral skeletal muscles in a mouse model for nebulin-based nemaline myopathy Open
View article: Mutation‐specific effects on thin filament length in thin filament myopathy
Mutation‐specific effects on thin filament length in thin filament myopathy Open
Objective Thin filament myopathies are among the most common nondystrophic congenital muscular disorders, and are caused by mutations in genes encoding proteins that are associated with the skeletal muscle thin filament. Mechanisms underly…
View article: <scp><i>TPM</i></scp><i>3</i> deletions cause a hypercontractile congenital muscle stiffness phenotype
<span><i>TPM</i></span><i>3</i> deletions cause a hypercontractile congenital muscle stiffness phenotype Open
Objective Mutations in TPM3 , encoding Tpm3.12, cause a clinically and histopathologically diverse group of myopathies characterized by muscle weakness. We report two patients with novel de novo Tpm3.12 single glutamic acid deletions at po…
View article: Muscle weakness in<i>TPM3</i>-myopathy is due to reduced Ca<sup>2+</sup>-sensitivity and impaired acto-myosin cross-bridge cycling in slow fibres
Muscle weakness in<i>TPM3</i>-myopathy is due to reduced Ca<sup>2+</sup>-sensitivity and impaired acto-myosin cross-bridge cycling in slow fibres Open
Dominant mutations in TPM3, encoding α-tropomyosinslow, cause a congenital myopathy characterized by generalized muscle weakness. Here, we used a multidisciplinary approach to investigate the mechanism of muscle dysfunction in 12 TPM3-myop…
View article: Effect of levosimendan on the contractility of muscle fibers from nemaline myopathy patients with mutations in the nebulin gene
Effect of levosimendan on the contractility of muscle fibers from nemaline myopathy patients with mutations in the nebulin gene Open
View article: Force-Sarcomere Length Relations in Patients with Thin Filament Myopathy Caused by Mutations in NEB, ACTA1, TPM2, TPM3, KBTBD13, KLHL40 and KLHL41
Force-Sarcomere Length Relations in Patients with Thin Filament Myopathy Caused by Mutations in NEB, ACTA1, TPM2, TPM3, KBTBD13, KLHL40 and KLHL41 Open