Zhiyong Chen, Monica Saini, Jasmine S Koh, Kalpana Prasad, Swee Hoon Koh, Karine S S Tay, Ming Lee, Yi Jayne Tan, Adeline S L Ng, Stacey Kiat Hong Tay, Kong Bing Tan, Ankit Tandon, Jeane M M Tan, Josiah Y H Chai
AIM: We describe a cohort of five patients with limb-girdle muscular dystrophy (LGMD) 2G/LGMD-R7 in a South-east Asian cohort. BACKGROUND: LGMD2G/LGMD-R7-telethonin-related is caused by mutations in the TCAP gene that encodes for telethonin. METHODS: We identified consecutive patients with LGMD2G/LGMD-R7-telethonin-related, diagnosed at the National Neuroscience Institute (NNI) and National University Hospital (NUH) between January 2000 and June 2021...
November 28, 2022: Journal of Neuromuscular Diseases
Bo Wu, Morgan Drains, Sapana N Shah, Pei Juan Lu, Victoria Leroy, Jessalyn Killilee, Raegan Rawls, Jason D Tucker, Anthony Blaeser, Qi Long Lu
Limb Girdle Muscular Dystrophy 2I (LGMDR9) is one of the most common LGMD characterized by defects in glycosylation of α-dystroglycan (matriglycan) resulting from mutations of Fukutin-related protein (FKRP). There is no effective therapy currently available. We recently demonstrated that ribitol supplement increases levels of matriglycan in cells in vitro and in FKRP-P448L (P448L) mutant mouse model through drinking water administration. To be clinically relevant, we have now conducted a dose-escalating efficacy study by gavage in P448L mutant mice...
2022: PloS One
Zoe White, Zeren Sun, Elodie Sauge, Dan Cox, Graham Donen, Dmitri Pechkovsky, Volker Straub, Gordon A Francis, Pascal Bernatchez
Limb-girdle muscular dystrophy (MD) type 2B (LGMD2B) and Duchenne MD (DMD) are caused by mutations to the Dysferlin and Dystrophin genes, respectively. We have recently demonstrated in typically mild dysferlin- and dystrophin-deficient mouse models that increased plasma cholesterol levels severely exacerbate muscle wasting, and that DMD patients display primary dyslipidemia characterized by elevated plasma cholesterol and triglycerides. Herein, we investigate lipoprotein abnormalities in LGMD2B and if statin therapy protects dysferlin-deficient mice (Dysf) from muscle damage...
November 29, 2022: Skeletal Muscle
Haiwen Li, Peipei Wang, Ethan Hsu, Kelsey M Pinckard, Kristin I Stanford, Renzhi Han
Limb-girdle muscular dystrophy type R25 (LGMDR25) is caused by recessive mutations in BVES encoding a cAMP binding protein, characterized by progressive muscular dystrophy with deteriorating muscle function and impaired cardiac conduction in patients. There is currently no therapeutic treatment for LGMDR25 patients. Here we report the efficacy and safety of recombinant adeno-associated virus 9 (AAV9)-mediated systemic delivery of human BVES driven by a muscle-specific promoter MHCK7 (AAV9.BVES) in BVES-knockout (BVES-KO) mice...
November 24, 2022: Molecular Therapy
Andrew R Findlay, Sarah E Robinson, Stephanie Poelker, Michelle Seiffert, Rocio Bengoechea, Conrad C Weihl
OBJECTIVE: To delineate the full phenotypic spectrum and characterize the natural history of limb girdle muscular dystrophy type D1 (LGMDD1). METHODS: We extracted age at clinical events of interest contributing to LGMDD1 disease burden via a systematic literature and chart review. Manual muscle testing and quantitative dynamometry data were used to estimate annualized rates of change. We also conducted a cross-sectional observational study using previously validated patient-reported outcome assessments (ACTIVLIM, PROMIS-57) and a new LGMDD1 questionnaire...
November 25, 2022: Annals of Clinical and Translational Neurology
Grace Bryant, Steven A Moore, James S Nix, Grace Rice, Murat Gokden, Aravindhan Veerapandiyan
Dysferlinopathies are a group of phenotypically heterogeneous disorders caused by pathogenic variants in the DYSF (DYStrophy-associated Fer-1-like) gene encoding dysferlin. The phenotypic spectrum includes Miyoshi muscular dystrophy (MMD), limb-girdle muscular dystrophy type R2, distal myopathy with anterior tibial onset, and isolated hyperCKemia. MMD is characterized by muscle weakness and atrophy predominantly affecting the calf muscles with symptoms onset between 14 and 40 years of age. There is no clear phenotype - genotype correlation for dysferlinopathy...
2022: Child Neurology Open
Leema Reddy Peddareddygari, Kinsi Oberoi, Raji P Grewal
We report a genotype-phenotype analysis of a family in which a titinopathy is transmitted in an autosomal dominant pattern. In this family, following neurological history and examination, electromyogram, and muscle biopsy, the diagnosis of limb-girdle muscular dystrophy with contractures was made in an affected mother and son. Genetic testing employing the whole exome was performed and revealed two variants in the TTN gene, c.712G>C, p. Glu238Gln and c.1397A>C, p.Gln466Arg, which segregated with the disease in the affected mother-son duo but not in an unaffected sibling...
October 2022: Curēus
Michelle Wintzinger, Karen Miz, Allen York, Alexis R Demonbreun, Jeffery D Molkentin, Elizabeth M McNally, Mattia Quattrocelli
In vivo testing of glucocorticoid steroids in dystrophic mice offers important insights in benefits and risks of those drugs in the pathological context of muscular dystrophy. Frequency of dosing changes the spectrum of glucocorticoid effects on muscle and metabolic homeostasis. Here, we describe a combination of non-invasive and invasive methods to quantitatively discriminate the specific effects of intermittent (once-weekly) versus mainstay (once-daily) regimens on muscle fibrosis, muscle function, and metabolic homeostasis in murine models of Duchenne and limb-girdle muscular dystrophies...
2023: Methods in Molecular Biology
Saeed Anwar, Toshifumi Yokota
Dysferlinopathies are a group of disabling muscular dystrophies  that includes limb girdle muscular dystrophy type 2B (LGMD2B), Miyoshi myopathy, and distal myopathy with anterior tibial onset (DMAT) as the main phenotypes. They are associated with molecular defects in DYSF, which encodes dysferlin, a key player in sarcolemmal homeostasis. Previous investigations have suggested that exon skipping may be a promising therapy for many patients with dysferlinopathies. It was reported that exons 28-29 of DYSF are dispensable for dysferlin functions...
2023: Methods in Molecular Biology
Viviane Tran, Sarah Nahlé, Amélie Robert, Inès Desanlis, Ryan Killoran, Sophie Ehresmann, Marie-Pier Thibault, David Barford, Kodi S Ravichandran, Martin Sauvageau, Matthew J Smith, Marie Kmita, Jean-François Côté
Myoblast fusion is fundamental for the development of multinucleated myofibers. Evolutionarily conserved proteins required for myoblast fusion include RAC1 and its activator DOCK1. In the current study we analyzed the contribution of the DOCK1-interacting ELMO scaffold proteins to myoblast fusion. When Elmo1-/- mice underwent muscle-specific Elmo2 genetic ablation, they exhibited severe myoblast fusion defects. A mutation in the Elmo2 gene that reduced signaling resulted in a decrease in myoblast fusion. Conversely, a mutation in Elmo2 coding for a protein with an open conformation increased myoblast fusion during development and in muscle regeneration...
November 18, 2022: Nature Communications
Joshua L Hagedorn, Taylor M Dunn, Sajag Bhattarai, Carrie Stephan, Katherine D Mathews, Wanda Pfeifer, Arlene V Drack
BACKGROUND: Dystroglycanopathies are a heterogeneous group of membrane-related muscular dystrophies. The dystroglycanopathy phenotype includes a spectrum of severity ranging from severe congenital muscular dystrophy to adult-onset limb-girdle muscular dystrophy (LGMD). LGMDR9 is a dystroglycanopathy caused by mutations in the FKRP gene. Previous studies have characterized electroretinogram findings of dystroglycanopathy mouse models but have not been reported in humans. PURPOSE: This study set out to characterize the electroretinogram in eight participants with LGMDR9...
November 18, 2022: Documenta Ophthalmologica. Advances in Ophthalmology
Jing Tang, Jia-Peng Zhang, Xue-Jun Yang, Jing-Zi Zhong, Yan-Shu Xie, Qi Meng, Dan Lan
OBJECTIVES: To summarize the skeletal muscle magnetic resonance imaging (MRI) features of the lower limbs in common subtypes of muscular dystrophy (MD) and the experience in the application of MRI in the diagnosis of MD. METHODS: A total of 48 children with MD who were diagnosed by genetic testing were enrolled as subjects. The muscle MRI features of the lower limbs were analyzed. Cumulative fatty infiltration score was calculated for each subtype, and the correlation of cumulative fatty infiltration score with clinical indices was analyzed for Duchenne muscular dystrophy (DMD)...
November 15, 2022: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
Baiba Lace, Ieva Micule, Viktorija Kenina, Signe Setlere, Jurgis Strautmanis, Inese Kazaine, Gita Taurina, Daiga Murmane, Ieva Grinfelde, Liene Kornejeva, Zita Krumina, Olga Sterna, Ilze Radovica-Spalvina, Inta Vasiljeva, Linda Gailite, Janis Stavusis, Diana Livcane, Dita Kidere, Ieva Malniece, Inna Inashkina
Background and Objectives: Genetic testing has become an integral part of health care, allowing the confirmation of thousands of hereditary diseases, including neuromuscular disorders (NMDs). The reported average prevalence of individual inherited NMDs is 3.7-4.99 per 10,000. This number varies greatly in the selected populations after applying population-wide studies. The aim of this study was to evaluate the effect of genetic analysis as the first-tier test in patients with NMD and to calculate the disease prevalence and allelic frequencies for reoccurring genetic variants...
June 2022: Neurology. Genetics
Sagar Devkota, Sangeeta Shrestha, Tara Gurung, Saurav Shrestha
Regional anesthesia can be a very safe option in patients with limb girdle muscular dystrophy undergoing lower abdominal surgeries as general anesthesia and volatile anesthetic agents are associated with increased risk of malignant hyperthermia and rhabdomyolysis.
November 2022: Clinical Case Reports
Jun Hee Choi, Seung Yeon Jeong, Jooho Kim, Jin Seok Woo, Eun Hui Lee
Mutations in tripartite motif-containing protein 32 (TRIM32), especially in NHL repeats, have been found in skeletal muscle in patients with type 2H limb-girdle muscular dystrophy (LGMD2H). However, the roles of the NHL repeats of TRIM32 in skeletal muscle functions have not been well addressed. In the present study, to examine the functional role(s) of the TRIM32 NHL repeats in skeletal muscle, TRIM32-binding proteins in skeletal muscle were first searched using a binding assay and MALDI-TOF/TOF. Sarcoplasmic/endoplasmic reticulum Ca2+ -ATPase 1a (SERCA1a) was found to be a TRIM32-binding protein...
November 14, 2022: American Journal of Physiology. Cell Physiology
Hamidreza Mianesaz, Safoura Ghalamkari, Mansoor Salehi, Mahdiyeh Behnam, Majid Hosseinzadeh, Keivan Basiri, Majid Ghasemi, Maryam Sedghi, Behnaz Ansari
BACKGROUND: Limb-girdle muscular dystrophy (LGMD) is a non-syndromic muscular dystrophy caused by variations in the genes involved in muscle structure, function and repair. The heterogeneity in the severity, progression, age of onset, and causative genes makes next-generation sequencing (NGS) a necessary approach for the proper diagnosis of LGMD. METHODS: In this article, 26 Iranian patients with LGMD criteria were diagnosed with disease variants in the genes encoding calpain3, dysferlin, sarcoglycans and Laminin α-2...
November 14, 2022: Molecular Genetics & Genomic Medicine
Tanya Stojkovic, Marion Masingue, Corinne Métay, Norma B Romero, Bruno Eymard, Rabah Ben Yaou, Laetitia Rialland, Séverine Drunat, Corine Gartioux, Isabelle Nelson, Valérie Allamand, Gisèle Bonne, Rocio Nur Villar-Quiles
We report three siblings from a non-consanguineous family presenting a with contractural limb-girdle phenotype with intrafamilial variability. Muscle MRI showed posterior thigh and quadriceps involvement with a sandwich-like sign. Whole-exome sequencing identified two compound heterozygous missense TTN variants and one heterozygous LAMA2 variant. Brain MRI performed because of concentration difficulties in one of the siblings evidenced white-matter abnormalities, subsequently found in the others. The genetic analysis was re-oriented, revealing a novel pathogenic intronic LAMA2 variant which confirmed the LAMA2-RD diagnosis...
November 11, 2022: Journal of Neuromuscular Diseases
Mengge Yang, Suqiong Ji, Li Xu, Qing Zhang, Yue Li, Huajie Gao, Bitao Bu
BACKGROUND: Limb-girdle muscular dystrophy R2 (LGMD R2) is most frequently misdiagnosed as immune-mediated necrotizing myopathy (IMNM). This study aimed to compare the clinicopathological data of IMNM and LGMD R2 to find distinguishing features. METHODS: We retrospectively reassessed the medical data of patients with IMNM ( n = 41) and LGMD R2 ( n = 8) treated at Tongji Hospital from January 2017 to December 2021. RESULTS: In our cohort, patients with LGMD R2 had a longer interval of onset to first visit, mild muscle weakness with late upper limb involvement, less myalgia, no cervical muscle weakness or dysphagia, no extramuscular organs affected except cardiac involvement, and lack of various autoantibodies, such as antinuclear antibodies...
November 5, 2022: Journal of Clinical Medicine
Elena Zinina, Maria Bulakh, Alena Chukhrova, Oksana Ryzhkova, Peter Sparber, Olga Shchagina, Aleksander Polyakov, Sergey Kutsev
Duchenne/Becker muscular dystrophy (DMD/BMD) is the most common form of muscular dystrophy, accounting for over 50% of all cases. In this regard, in Russia we carry out a program of selective screening for DMD/BMD, which mainly involves male patients. The main inclusion criteria are an increase in the level of creatine phosphokinase (>2000 U/L) or an established clinical diagnosis. At the first stage of screening, patients are scanned for extended deletions and duplications in the DMD gene using multiplex ligase-dependent probe amplification (MLPA SALSA P034 and P035 DMD probemix, MRC-Holland)...
October 22, 2022: International Journal of Molecular Sciences
Uğur Aksu, Mehmet Hakan Uzun
Limb-girdle muscular dystrophy (LGMD) is a heterogeneous inherited disorder affecting the skeletal muscle and frequently also involve the heart and in LGMD; development of dilated cardiomyopathy is common and usually the predominant feature. Arrhythmias and conduction disease can be associated with the development of cardiomyopathy.
November 2022: Journal of Clinical Ultrasound: JCU
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