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Ichizo Nishino - One of the best experts on this subject based on the ideXlab platform.
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thigh muscle mri findings in Myopathy associated with anti mitochondrial antibody
Muscle & Nerve, 2019Co-Authors: Sumio Minamiyama, Sakiho Ueda, Hodaka Yamakado, Yusuke Sakato, Ryota Fujimoto, Hirofumi Yamashita, Nobukatsu Sawamoto, Ichizo Nishino, Ran Nakashima, Makoto UrushitaniAbstract:INTRODUCTION: Myopathy associated with anti-mitochondrial antibody (AMA) has recently been characterized as a distinct type of idiopathic inflammatory Myopathy. The purpose of this study is to evaluate the pattern of involvement in thigh muscles in AMA Myopathy using MRI. METHODS: Six patients with AMA Myopathy were identified and their muscle MRI findings evaluated. RESULTS: On thigh muscle MRI, all six patients showed high signal intensity with short-tau inversion recovery that reflected disease activity mostly in the adductor magnus, called a "cuneiform sign." Fatty degeneration was also prominent in the adductor magnus, as well as the semimembranosus muscles. DISCUSSION: These characteristic changes on MRI contrast with those of other inflammatory myopathies. From these observations, we concluded that the localization pattern of the inflammatory changes in muscle MRI can contribute to the diagnosis of AMA Myopathy.
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sialic acid replacement therapy for distal Myopathy with rimmed vacuoles
Brain and nerve, 2015Co-Authors: Madoka Moriyoshimura, Ichizo NishinoAbstract:: Distal Myopathy with rimmed vacuoles or GNE Myopathy, is an early adult-onset Myopathy with slow progression that preferentially affects the tibialis anterior muscle. Severely affected patients show marked limb muscle atrophy together with respiratory dysfunction. The disease is caused by a mutation in the GNE gene that catalyzes two rate-limiting reactions in cytosolic sialic acid synthesis. Oral treatment with sialic acid metabolite prevents muscle atrophy and weakness in a mouse GNE Myopathy model and a global Phase III study is currently underway. In addition, a global patient registry of neuromuscular cases is widely accepted as a useful tool to obtain epidemiological data and bolster patient recruitment for further development of this treatment strategy.
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respiratory dysfunction in patients severely affected by gne Myopathy distal Myopathy with rimmed vacuoles
Neuromuscular Disorders, 2012Co-Authors: Madoka Moriyoshimura, Ichizo Nishino, S. Noguchi, Yukiko K Hayashi, Miho MurataAbstract:Abstract GNE Myopathy is a rare and mildly progressive autosomal recessive Myopathy caused by GNE mutations. Respiratory dysfunction has not been reported in GNE Myopathy patients. In this study, we retrospectively reviewed the respiratory function of 39 severely affected GNE Myopathy patients (13 men, 26 women) from medical records, and compared these parameters with various other patient characteristics (e.g., GNE mutations, age at onset, creatine kinase levels, and being wheelchair-bound) for correlations. The mean % forced vital capacity [FVC] was 92 (26) (range, 16–128). In 12/39 (31%) patients, %FVC was p N -acetylmannosamine kinase domain exhibited lower %FVC, while only one compound heterozygous patient with separate mutations in the uridinediphosphate- N -acetylglucosamine 2-epimerase and the N -acetylmannosamine kinase domains had respiratory dysfunction. Our results collectively suggest that GNE Myopathy can cause severe respiratory failure. Respiratory dysfunction should be carefully monitored in patients with advanced GNE Myopathy characterized by early onset and homozygous homozygous mutations in the N -acetylmannosamine kinase domain.
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G.P.124 Fiber type disproportion caused by LMNA mutations
Neuromuscular Disorders, 2012Co-Authors: S. Kajino, Yuichi Hayashi, Keiko Ishigaki, Ikuya Nonaka, Makiko Osawa, Ichizo NishinoAbstract:Abstract Mutations in the gene encoding nuclear envelope proteins of A-type lamins ( LMNA ) are known to cause Emery–Dreifuss muscular dystrophy, limb girdle muscular dystrophy type 1B, and LMNA -related congenital muscular dystrophy. Pathological features of LMNA -Myopathy are nonspecific dystrophic changes including variation in fiber size, necrotic and regenerating process, and increased muscle fibers with internal nuclei. Congenital fiber type disproportion (CFTD) is a congenital Myopathy pathologically designated by smaller sized type 1 fibers at least 12% than type 2 fibers with no structural abnormalities. We recently came across a LMNA -Myopathy patient whose earlier diagnosis was CFTD. In this study, we searched for LMNA mutations in 94 unrelated patients pathologically diagnosed as CFTD. Genetically confirmed 29 LMNA -Myopathy patients were also reevaluated pathologically. We identified two patients carrying a novel heterozygous LMNA mutation (p.Glu33del or p.Lys123del) among 94 CFTD patients. On the other hand, 5 of 29 (17%) LMNA -Myopathy patients showed fiber type disproportion (FTD) on muscle pathology. The age at onset of the 7 LMNA -Myopathy patients with FTD was from 1y2m to 4y (mean 2y8m) except for one adult-onset patient. None of the LMNA -Myopathy patients with FTD had high arched palate or respiratory involvement. Serum creatine kinase levels were mildly elevated (mean 915□} 698 IU/L). The ratio of fiber size disproportion (%FSD) was not significantly different between LMNA -Myopathy withFTD and 9 CFTD patients with ACTA1 or TPM3 mutations. Importantly, CFTD with ACTA1 or TPM3 mutations showed type 1 fiber atrophy compared to age-matched controls, while LMNA -Myopathy with FTD showed type 2 fiber hypertrophy. From our results, we encourage LMNA mutation analysis in CFTD patients with no high arched palate and respiratory involvement.
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recent advances in distal Myopathy with rimmed vacuoles dmrv or hibm treatment perspectives
Current Opinion in Neurology, 2008Co-Authors: May Christine V. Malicdan, S. Noguchi, Ichizo NishinoAbstract:Purpose of reviewDistal Myopathy with rimmed vacuoles or hereditary inclusion body Myopathy is an adult-onset autosomal recessive, slowly progressive and debilitating Myopathy due to mutations in the gene that regulates the synthesis of sialic acid. This review aims to update our knowledge of this m
Nigel G Laing - One of the best experts on this subject based on the ideXlab platform.
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adult onset distal and proximal Myopathy with complete ophthalmoplegia associated with a novel de novo p leu1877pro mutation in myh2
Clinical Genetics, 2015Co-Authors: Macarena Cabreraserrano, V Fabian, J Boutilier, C Wise, Fathimath Faiz, P J Lamont, Nigel G LaingAbstract:: An MYH2 mutation p.(Glu706Lys) was originally described in a family with autosomal dominant inheritance, where the affected family members presented with multiple congenital contractures and ophthalmoplegia, progressing to a proximal Myopathy in adulthood. Another patient with a dominant mutation p.(Leu1870Pro) was described, presenting as a congenital Myopathy with ophthalmoplegia. Here, we present a patient with symptoms beginning at age 16 years, of prominent distal but also proximal weakness, bulbar involvement and ophthalmoplegia. Initially, clinically classified as oculopharyngodistal Myopathy, the patient was found to carry a novel, de novo MYH2 mutation c.5630T>C p.(Leu1877Pro). This expands the phenotype of dominant MYH2 myopathies with the clinical phenotype overlapping the oculopharyngodistal Myopathy spectrum.
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distal myosin heavy chain 7 Myopathy due to the novel transition c 5566g a p e1856k with high interfamilial cardiac variability and putative anticipation
Neuromuscular Disorders, 2014Co-Authors: Josef Finsterer, Claudia Stöllberger, Nigel G Laing, Oliver Brandau, William Wallefeld, Franco LacconeAbstract:Abstract Myosin-heavy-chain 7 (MYH7)-Myopathy manifests clinically with a distal, scapuloperoneal, limb-girdle (proximal), or axial distribution and may involve the respiratory muscles. Cardiac involvement is frequent, ranging from relaxation impairment to severe dilative cardioMyopathy. Progression and earlier onset of cardiac disease in successive generations with MYH7-Myopathy is unreported. In a five-generation family MYH7-Myopathy due to the novel c.5566G > A (p.E1856 K) mutation manifested with late-onset, distal > proximal Myopathy and variable degree of cardiac involvement. The index patient developed distal Myopathy since age 49 y and anginal chest pain. Her mother had distal Myopathy and impaired myocardial relaxation. The daughter of the index patient had discrete Myopathy but left ventricular hypertrabeculation/noncompaction and ventricular arrhythmias requiring an implantable cardioverter defibrillator. The granddaughter of the index patient had infantile dilated cardioMyopathy without overt Myopathy. Cardiac involvement may be present in MYH7-Myopathy and may be progressive between the generations, ranging from relaxation abnormality to noncompaction, ventricular arrhythmias, and dilated cardioMyopathy.
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Congenital myopathies (Journal Article)
Current opinion in neurology, 2007Co-Authors: Nigel G LaingAbstract:The aim of this review is to provide an up-to-date personal analysis of current congenital Myopathy research. In the past year novel congenital myopathies have been suggested, genes have been discovered for some of the congenital myopathies for the first time (beta-tropomyosin in cap disease and perhaps skeletal muscle alpha-actin in Zebra body Myopathy), further genes have been identified for congenital myopathies where other genes had already been found (cofilin in nemaline Myopathy, selenoprotein N in congenital fibre type disproportion) and recessive myosin storage Myopathy was associated with homozygous mutation of slow-skeletal/beta-cardiac myosin which was already known to be mutated in dominant myosin storage Myopathy. There has been further clarification of the pathobiology of the congenital myopathies, including determination of the basis of epigenetic effects: silencing of the normal allele in recessive central core disease and persistence of cardiac (fetal) alpha-actin in nemaline Myopathy patients with no skeletal actin. The increased understanding of the genes and pathobiology of the congenital myopathies that is developing should ultimately lead to effective treatments.
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actin mutations are one cause of congenital fibre type disproportion
Annals of Neurology, 2004Co-Authors: Nigel G Laing, Nigel F Clarke, Khema Liyanage, K R Walker, Yasuaki Kobayashi, Shuichi Shimakawa, Tohru Hagiwara, Robert A Ouvrier, John C Sparrow, Ichizo NishinoAbstract:We report three heterozygous missense mutations of the skeletal muscle alpha actin gene (ACTA1) in three unrelated cases of congenital fiber type disproportion (CFTD) from Japan and Australia. This represents the first genetic cause of CFTD to be identified and confirms that CFTD is genetically heterogeneous. The three mutations we have identified Leucine221Proline, Aspartate292Valine, and Proline332Serine are novel. They have not been found previously in any cases of nemaline, actin, intranuclear rod, or rod-core Myopathy caused by mutations in ACTA1. It remains unclear why these mutations cause type 1 fiber hypotrophy but no nemaline bodies. The three mutations all lie on one face of the actin monomer on the surface swept by tropomyosin during muscle activity, which may suggest a common pathological mechanism. All three CFTD cases with ACTA1 mutations had severe congenital weakness and respiratory failure without ophthalmoplegia. There were no clinical features specific to CFTD cases with ACTA1 mutations, but the presence of normal eye movements in a severe CFTD patient may be an important clue for the presence of a mutation in ACTA1. Ann Neurol 2004;56:689 – 694 Congenital fiber type disproportion is a rare form of congenital Myopathy that was first identified in 1973. Michael Brooke used the term to describe 12 children with early-onset generalized weakness and type 1 (slow twitch) muscle fibers that were at least 12% smaller than type 2 (fast twitch) fibers. 1 It is clear that this histological appearance can be seen in other neuromuscular conditions, and care must be taken to exclude other known causes. 2 Until now, the genetic basis of congenital fiber type disproportion (CFTD) has been unknown but heterogeneity in the clinical phenotype and inheritance patterns has pointed to there being more than one cause. 2 Nemaline Myopathy is a different congenital Myopathy characterized by the presence of nemaline bodies in muscle fibers. Mutations in five genes encoding sarcomeric thin filament proteins have been shown to cause nemaline Myopathy. These genes encode -tropomyosin slow (TPM3), -tropomyosin (TPM2), -skeletal actin (ACTA1), nebulin (NEB), and troponin T slow (TNNT1). 3 CFTD and nemaline Myopathy may share clinical features and relative type 1 fiber smallness has been reported in many patients with nemaline Myopathy. 4–6 In addition, nemaline Myopathy patients may have rods in one muscle, but not another, and some nemaline Myopathy patients have been diagnosed only on finding nemaline bodies in a subsequent biopsy. 6 For these reasons, we consider all the genes that can cause nemaline Myopathy as candidate genes for CFTD and elected to examine -skeletal actin in CFTD cases, because it is the easiest nemaline Myopathy gene to screen for mutations and is mutated in approximately 20% of nemaline Myopathy cases. 7
Claudia Stöllberger - One of the best experts on this subject based on the ideXlab platform.
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Arrhythmogenic Right Ventricular Dysplasia in Neuromuscular Disorders.
Clinical Medicine Insights. Cardiology, 2016Co-Authors: Josef Finsterer, Claudia StöllbergerAbstract:Arrhythmogenic right ventricular dysplasia (ARVD) is a rare, genetic disorder predominantly affecting the right ventricle. There is increasing evidence that in some cases, ARVD is due to mutations in genes, which have also been implicated in primary myopathies. This review gives an overview about Myopathy-associated ARVD and how these patients can be managed. A literature review was done using appropriate search terms. The Myopathy, which is most frequently associated with ARVD, is the myofibrillar Myopathy due to desmin mutations. Only in a single patient, ARVD was described in myotonic dystrophy type 1. However, there are a number of genes causing either Myopathy or ARVD. These genes include lamin A/C, ZASP/cypher, transmembrane protein-43, titin, and the ryanodine receptor-2 gene. Diagnosis and treatment are identical for Myopathy-associated ARVD and nonMyopathy-associated ARVD. Patients with primary Myopathy due to mutations in the desmin, dystrophia myotonica protein kinase, lamin A/C, ZASP/cypher, transmembrane protein-43, titin, or the ryanodine receptor-2 gene should be screened for ARVD. Patients carrying a pathogenic variant in any of these genes should undergo annual cardiological investigations for cardiac function and arrhythmias.
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Arrhythmogenic Right Ventricular Dysplasia in Neuromuscular Disorders
2016Co-Authors: Josef Finsterer, Claudia StöllbergerAbstract:Objectives: Arrhythmogenic right ventricular dysplasia (ARVD) is a rare, genetic disorder predominantly affecting the right ventricle. There is increasing evidence that in some cases, ARVD is due to mutations in genes, which have also been implicated in primary myopathies. This review gives an overview about Myopathy-associated ARVD and how these patients can be managed. Methods: A literature review was done using appropriate search terms. Results: The Myopathy, which is most frequently associated with ARVD, is the myofibrillar Myopathy due to desmin mutations. Only in a single patient, ARVD was described in myotonic dystrophy type 1. However, there are a number of genes causing either Myopathy or ARVD. These genes include lamin A/C, ZASP/cypher, transmembrane protein-43, titin, and the ryanodine receptor-2 gene. Diagnosis and treatment are identical for Myopathy-associated ARVD and nonMyopathy-associated ARVD. Conclusions: Patients with primary Myopathy due to mutations in the desmin, dystrophia myotonica protein kinase, lamin A/C, ZASP/cypher, transmembrane protein-43, titin, or the ryanodine receptor-2 gene should be screened for ARVD. Patients carrying a pathogenic variant in any of these genes should undergo annual cardiological investigations for cardiac function and arrhythmias.
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distal myosin heavy chain 7 Myopathy due to the novel transition c 5566g a p e1856k with high interfamilial cardiac variability and putative anticipation
Neuromuscular Disorders, 2014Co-Authors: Josef Finsterer, Claudia Stöllberger, Nigel G Laing, Oliver Brandau, William Wallefeld, Franco LacconeAbstract:Abstract Myosin-heavy-chain 7 (MYH7)-Myopathy manifests clinically with a distal, scapuloperoneal, limb-girdle (proximal), or axial distribution and may involve the respiratory muscles. Cardiac involvement is frequent, ranging from relaxation impairment to severe dilative cardioMyopathy. Progression and earlier onset of cardiac disease in successive generations with MYH7-Myopathy is unreported. In a five-generation family MYH7-Myopathy due to the novel c.5566G > A (p.E1856 K) mutation manifested with late-onset, distal > proximal Myopathy and variable degree of cardiac involvement. The index patient developed distal Myopathy since age 49 y and anginal chest pain. Her mother had distal Myopathy and impaired myocardial relaxation. The daughter of the index patient had discrete Myopathy but left ventricular hypertrabeculation/noncompaction and ventricular arrhythmias requiring an implantable cardioverter defibrillator. The granddaughter of the index patient had infantile dilated cardioMyopathy without overt Myopathy. Cardiac involvement may be present in MYH7-Myopathy and may be progressive between the generations, ranging from relaxation abnormality to noncompaction, ventricular arrhythmias, and dilated cardioMyopathy.
Josef Finsterer - One of the best experts on this subject based on the ideXlab platform.
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Arrhythmogenic Right Ventricular Dysplasia in Neuromuscular Disorders.
Clinical Medicine Insights. Cardiology, 2016Co-Authors: Josef Finsterer, Claudia StöllbergerAbstract:Arrhythmogenic right ventricular dysplasia (ARVD) is a rare, genetic disorder predominantly affecting the right ventricle. There is increasing evidence that in some cases, ARVD is due to mutations in genes, which have also been implicated in primary myopathies. This review gives an overview about Myopathy-associated ARVD and how these patients can be managed. A literature review was done using appropriate search terms. The Myopathy, which is most frequently associated with ARVD, is the myofibrillar Myopathy due to desmin mutations. Only in a single patient, ARVD was described in myotonic dystrophy type 1. However, there are a number of genes causing either Myopathy or ARVD. These genes include lamin A/C, ZASP/cypher, transmembrane protein-43, titin, and the ryanodine receptor-2 gene. Diagnosis and treatment are identical for Myopathy-associated ARVD and nonMyopathy-associated ARVD. Patients with primary Myopathy due to mutations in the desmin, dystrophia myotonica protein kinase, lamin A/C, ZASP/cypher, transmembrane protein-43, titin, or the ryanodine receptor-2 gene should be screened for ARVD. Patients carrying a pathogenic variant in any of these genes should undergo annual cardiological investigations for cardiac function and arrhythmias.
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Arrhythmogenic Right Ventricular Dysplasia in Neuromuscular Disorders
2016Co-Authors: Josef Finsterer, Claudia StöllbergerAbstract:Objectives: Arrhythmogenic right ventricular dysplasia (ARVD) is a rare, genetic disorder predominantly affecting the right ventricle. There is increasing evidence that in some cases, ARVD is due to mutations in genes, which have also been implicated in primary myopathies. This review gives an overview about Myopathy-associated ARVD and how these patients can be managed. Methods: A literature review was done using appropriate search terms. Results: The Myopathy, which is most frequently associated with ARVD, is the myofibrillar Myopathy due to desmin mutations. Only in a single patient, ARVD was described in myotonic dystrophy type 1. However, there are a number of genes causing either Myopathy or ARVD. These genes include lamin A/C, ZASP/cypher, transmembrane protein-43, titin, and the ryanodine receptor-2 gene. Diagnosis and treatment are identical for Myopathy-associated ARVD and nonMyopathy-associated ARVD. Conclusions: Patients with primary Myopathy due to mutations in the desmin, dystrophia myotonica protein kinase, lamin A/C, ZASP/cypher, transmembrane protein-43, titin, or the ryanodine receptor-2 gene should be screened for ARVD. Patients carrying a pathogenic variant in any of these genes should undergo annual cardiological investigations for cardiac function and arrhythmias.
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distal myosin heavy chain 7 Myopathy due to the novel transition c 5566g a p e1856k with high interfamilial cardiac variability and putative anticipation
Neuromuscular Disorders, 2014Co-Authors: Josef Finsterer, Claudia Stöllberger, Nigel G Laing, Oliver Brandau, William Wallefeld, Franco LacconeAbstract:Abstract Myosin-heavy-chain 7 (MYH7)-Myopathy manifests clinically with a distal, scapuloperoneal, limb-girdle (proximal), or axial distribution and may involve the respiratory muscles. Cardiac involvement is frequent, ranging from relaxation impairment to severe dilative cardioMyopathy. Progression and earlier onset of cardiac disease in successive generations with MYH7-Myopathy is unreported. In a five-generation family MYH7-Myopathy due to the novel c.5566G > A (p.E1856 K) mutation manifested with late-onset, distal > proximal Myopathy and variable degree of cardiac involvement. The index patient developed distal Myopathy since age 49 y and anginal chest pain. Her mother had distal Myopathy and impaired myocardial relaxation. The daughter of the index patient had discrete Myopathy but left ventricular hypertrabeculation/noncompaction and ventricular arrhythmias requiring an implantable cardioverter defibrillator. The granddaughter of the index patient had infantile dilated cardioMyopathy without overt Myopathy. Cardiac involvement may be present in MYH7-Myopathy and may be progressive between the generations, ranging from relaxation abnormality to noncompaction, ventricular arrhythmias, and dilated cardioMyopathy.
Angela Huebner - One of the best experts on this subject based on the ideXlab platform.
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nemaline Myopathy caused by mutations in the nebulin gene may present as a distal Myopathy
Neuromuscular Disorders, 2011Co-Authors: Vilma-lotta Lehtokari, Agnes Herczegfalvi, Veronika Karcagi, Julien Pouget, Jerome Franques, Dominique Figarellabranger, Katarina Pelin, Maja Von Der Hagen, Jean-françois Pellissier, Angela HuebnerAbstract:Mutations in the nebulin gene are the main cause of autosomal recessive nemaline Myopathy, with clinical presentations ranging from mild to severe disease. We have previously reported a nonspecific distal Myopathy caused by homozygous missense mutations in the nebulin gene in six Finnish patients from four different families. Here we describe three non-Finnish patients in two unrelated families with distal nemaline Myopathy caused by four different compound heterozygous nebulin mutations, only one of which is a missense mutation. One of the mutations has previously been identified in one family with the severe form of nemaline Myopathy. We conclude that nemaline Myopathy and distal Myopathy caused by nebulin mutations form a clinical and histological continuum. Nemaline Myopathy should be considered as a differential diagnosis in patients presenting with an early-onset predominantly distal Myopathy.
