Three novel MTM1 pathogenic variants identified in Japanese patients with X ‐linked myotubular myopathy

ConclusionsAll variants were assessed as “Class 4 (likely pathogenic)” on the basis of the guideline of American College of Medical Genetics and Genomics. These distinct pathological features among the patients with variants in the second cluster of PTP domain inMTM1 provides an insight into microheterogeneities in disease phenotypes in XLMTM.
Source: Molecular Genetics & Genomic Medicine - Category: Genetics & Stem Cells Authors: Tags: CLINICAL REPORT Source Type: research

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Condition:   Centronuclear Myopathy Intervention:   Drug: DYN101 Sponsor:   Dynacure SAS Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
CONCLUSION: Gene therapies have the potential to significantly influence the course of neuromuscular diseases. First positive intermediate results have been published and the first treatment has recently been approved in the USA. Long-term data on sustained effects and toxicity of gene therapies are not yet available. These novel treatment options will present new challenges for the healthcare systems concerning diagnosis, treatment and reimbursement. PMID: 31286145 [PubMed - as supplied by publisher]
Source: Der Nervenarzt - Category: Neurology Authors: Tags: Nervenarzt Source Type: research
Mutations in guanosine diphosphate mannose pyrophosphorylase B (GMPPB) have been found to cause a wide spectrum of neuromuscular syndromes, including congenital muscular dystrophy, limb girdle muscular dystrophy with or without cognitive impairment, recurrent rhabdomyolysis and congenital myasthenic syndrome (CMS) [1 –3]. Some patients also present with myopathy-CMS overlap phenotypes [2]. Like other CMS caused by defects of glycosylation, GMPPB-CMS typically affects limb girdle muscles, without significant ocular or bulbar weakness [4].
Source: Neuromuscular Disorders - Category: Neurology Authors: Tags: Case report Source Type: research
Abstract Introduction Genetic neuromuscular diseases (NMDs) constitute a heterogeneous group of rare conditions, including some of the most disabling conditions in childhood. Over the last decade, early diagnosis, multidisciplinary care and anticipatory treatment strategies have improved survival and quality of life of several conditions. Recently, advanced technologies have greatly expanded preclinical and clinical research, and specific therapies have been introduced for three diseases, namely enzyme replacement therapy for Pompe disease (PD), gene expression modulation and gene therapy for Duchenne muscular dys...
Source: Pharmacological Reviews - Category: Drugs & Pharmacology Authors: Tags: Expert Rev Clin Pharmacol Source Type: research
Publication date: Available online 25 April 2019Source: Neuroscience LettersAuthor(s): Chengfeng Xiao, Shuang Qiu, Xiao Li, Dan-Ju Luo, Gong-Ping LiuAbstractDrosophila egg-derived tyrosine phosphatase (EDTP), a lipid phosphatase that removes 3-position phosphate at the inositol ring, has dual functions in oogenesis and muscle performance in adults. A mammalian homologous gene MTMR14, which encodes the myotubularin-related protein 14, negatively regulates autophagy. Mutation of EDTP/MTMR14, however, causes at least three deleterious consequences: (1) the lethality in early embryogenesis in Drosophila; (2) a “jumpy&rdq...
Source: Neuroscience Letters - Category: Neuroscience Source Type: research
Abstract Skeletal muscle deficiency in the 3-phosphoinositide (PtdInsP) phosphatase myotubularin (MTM1) causes myotubular myopathy which is associated with severe depression of voltage-activated sarcoplasmic reticulum Ca2+ release through ryanodine receptors. In the present study we aimed at further understanding how Ca2+ release is altered in MTM1-deficient muscle fibers, at rest and during activation. While in wild-type muscle fibers, SR Ca2+ release exhibits fast stereotyped kinetics of activation and decay throughout the voltage range of activation, Ca2+ release in MTM1-deficient muscle fibers exhibits slow an...
Source: Cell Calcium - Category: Cytology Authors: Tags: Cell Calcium Source Type: research
Publication date: Available online 5 April 2019Source: Clinica Chimica ActaAuthor(s): Tomofumi Misaka, Akiomi Yoshihisa, Yasuchika TakeishiAbstractTitin, encoded by the gene TTN, is the largest human protein, and plays central roles in sarcomeric structures and functions in skeletal and cardiac muscles. Mutations of TTN are causally related to specific types of muscular dystrophies and cardiomyopathies. A developed methodology of next generation sequencing has recently led to the identification of novel TTN mutations in such diseases. The clinical significance of titin is now emerging as a target for genetic strategies. Ti...
Source: Clinica Chimica Acta - Category: Laboratory Medicine Source Type: research
Abstract Titin, encoded by the gene TTN, is the largest human protein, and plays central roles in sarcomeric structures and functions in skeletal and cardiac muscles. Mutations of TTN are causally related to specific types of muscular dystrophies and cardiomyopathies. A developed methodology of next generation sequencing has recently led to the identification of novel TTN mutations in such diseases. The clinical significance of titin is now emerging as a target for genetic strategies. Titin-related muscular dystrophies include tibial muscular dystrophy, limb-girdle muscular dystrophy, Emery-Dreifuss muscular dystr...
Source: International Journal of Clinical Chemistry - Category: Chemistry Authors: Tags: Clin Chim Acta Source Type: research
Centronuclear myopathies (CNMs) are severe diseases characterized by muscle weakness and myofiber atrophy. Currently, there are no approved treatments for these disorders. Mutations in the phosphoinositide 3-phosphatase myotubularin (MTM1) are responsible for X-linked CNM (XLCNM), also called myotubular myopathy, whereas mutations in the membrane remodeling Bin/amphiphysin/Rvs protein amphiphysin 2 [bridging integrator 1 (BIN1)] are responsible for an autosomal form of the disease. Here, we investigated the functional relationship between MTM1 and BIN1 in healthy skeletal muscle and in the physiopathology of CNM. Genetic o...
Source: Science Translational Medicine - Category: Biomedical Science Authors: Tags: Research Articles Source Type: research
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