Limb-girdle muscular dystrophy type 2A

An autosomal recessive form of muscular dystrophy primarily affecting the proximal muscles, resulting in difficulty walking. The age at onset varies, but typically occurs in childhood, and the disorder is progressive. Other features may include scapular winging, calf pseudohypertrophy, and CONTRACTURES. Mutations in the CAPN3 gene have been identified. OMIM: 253600

Also Known As:

Networked: 189 relevant articles (2 outcomes, 21 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Duchenne Muscular Dystrophy (Muscular Dystrophy, Becker)
2.	Dermatomyositis (Dermatopolymyositis)
3.	Inclusion Body Myositis
4.	Dysferlinopathy
5.	Limb-girdle muscular dystrophy type 2A

Experts

1.	Richard, Isabelle: 15 articles (01/2021 - 05/2003)
2.	Sorimachi, Hiroyuki: 12 articles (12/2014 - 07/2003)
3.	Ono, Yasuko: 11 articles (12/2014 - 01/2004)
4.	Vissing, John: 8 articles (01/2020 - 08/2008)
5.	Doi, Naoko: 8 articles (12/2014 - 01/2005)
6.	Spencer, Melissa J: 8 articles (09/2011 - 10/2003)
7.	Kramerova, Irina: 7 articles (01/2016 - 08/2005)
8.	Richard, I: 7 articles (05/2007 - 05/2000)
9.	Beckmann, J S: 7 articles (06/2002 - 05/2000)
10.	López de Munain, Adolfo: 6 articles (12/2019 - 01/2008)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Limb-girdle muscular dystrophy type 2A:

1.	CalpainIBA 02/01/2006 - "Safety and efficacy of AAV-mediated calpain 3 gene transfer in a mouse model of limb-girdle muscular dystrophy type 2A." 12/01/2020 - "From a therapeutic perspective, the autosomal recessive form of calpainopathy is quite suitable to gene replacement strategies; the viability of recombinant AAV-mediated calpain 3 transfer has been demonstrated in animal models and clinical trials are expected in the coming years. " 05/01/2010 - "We studied all the patients diagnosed in the neuromuscular center of Bordeaux (France) with confirmed calpainopathy in order to establish the appropriate diagnostic approach (inclusion criteria: muscular biopsy with calpain 3 western blot study, two mutations in CAPN3). " 07/21/2022 - "Genetic testing confirmed heterozygous calpain mutations consistent with limb girdle muscular dystrophy type 2A." 01/01/2020 - "A single c.1715G>C calpain 3 gene variant causes dominant calpainopathy with loss of calpain 3 expression and activity."
2.	Complement Membrane Attack Complex (Membrane Attack Complex)IBA 01/01/2022 - "Compared to calpainopathy, Becker muscular dystrophy, and inflammatory myopathies, the unique profile of minimal inflammatory cell infiltrates, absent to focal MHC class I, and diffuse myofiber complement C5b-9 deposition is the pathologic signature of dysferlinopathy muscle biopsies." 01/01/2022 - "In contrast, complement C5b-9 deposition was similar among dysferlinopathy, dermatomyositis, and inclusion body myositis biopsies but significantly greater than calpainopathy and Becker muscular dystrophy biopsies (p = 0.05). "
3.	Complement System Proteins (Complement)IBA 01/01/2022 - "Compared to calpainopathy, Becker muscular dystrophy, and inflammatory myopathies, the unique profile of minimal inflammatory cell infiltrates, absent to focal MHC class I, and diffuse myofiber complement C5b-9 deposition is the pathologic signature of dysferlinopathy muscle biopsies." 01/01/2022 - "In contrast, complement C5b-9 deposition was similar among dysferlinopathy, dermatomyositis, and inclusion body myositis biopsies but significantly greater than calpainopathy and Becker muscular dystrophy biopsies (p = 0.05). "
4.	Proteins (Proteins, Gene)FDA Link 07/01/2010 - "To study the frequency of LGMD2A in Indian population on the basis of protein analysis by immunoblotting and to correlate pathological and clinical features with protein analysis. " 07/01/2010 - "Limb girdle muscular dystrophy type 2A in India: a study based on semi-quantitative protein analysis, with clinical and histopathological correlation." 01/01/2007 - "This study provides the first evidence of the pathogenetic effect of specific CAPN3 gene mutations on the corresponding protein function in LGMD2A muscle and offers new insights into the structural-functional relationship of the gene and protein regions that are crucial for the autolytic activity of calpain-3." 03/01/2006 - "Moreover, our study expands the spectrum of calpainopathies to cases that simulate a neurogenic lesion in muscle biopsies, and the knowledge of possible secondary deficiencies of muscular proteins also contributes to a diagnosis of LGMD2A." 08/01/2005 - "These studies suggest that accumulation of aged and damaged proteins can lead to cellular toxicity and a cell stress response in C3KO muscles, and that these characteristics are pathological features of LGMD2A."
5.	DysferlinIBA 07/15/2013 - "A diagnosis of calpainopathy was made in 12 cases (17%), and dysferlin deficiency in 10 cases (15%). " 03/01/2006 - "Immunoblot analysis revealed the deficiency of p 94 in all genetically confirmed cases of LGMD2A, and secondary dysferlin deficiency was demonstrated on muscle membranes in 6 patients using immunofluorescence. " 10/01/2004 - "Further, we observed a reduction of dysferlin in muscle membrane in five of our seven LGMD2A patients by immunohistochemical analysis of muscle sections." 12/01/1999 - "We described eighteen mutations in the dysferlin gene with MM or limb-girdle muscular dystrophy type 2 B (LGMD 2 B). " 10/01/2019 - "Females with LGMD2B/LGMD-R2-dysferlin-related had less severe progression to handicap than males and LGMD2A/LGMD-R1-calpain3-related patients with truncating variants had earlier disease onset and more severe progression to handicap than patients without truncating variants. "
6.	Sarcoglycans (beta Sarcoglycan)IBA 05/01/2000 - "The classification of families was as follows: calpainopathy 7, dysferlinopathy 3, alpha sarcoglycan deficiency 2, beta sarcoglycan deficiency 7, gamma sarcoglycan deficiency 5, delta sarcoglycan deficiency 1, and merosinopathy 2. There were two families showing an Emery-Dreifuss phenotype and nine showing no linkage to the LGMD2A-F loci, and they had preserved sarcoglycans. " 05/01/1997 - "Mutations in the delta-sarcoglycan gene are a rare cause of autosomal recessive limb-girdle muscular dystrophy (LGMD2)." 12/01/1996 - "All patients with LGMD2A and 2B had a mild clinical course while those with a primary sarcoglycan mutation (LGMD2C to 2F) had a range of clinical severity. " 07/01/1995 - "Four genes causing AR LGMD have been mapped: the 15q (LGMD2a), the 2p (LGMD2b), the 13q locus (LGMD2c) and the adhalin gene on chromosome 17q (LGMD2d). " 08/01/1997 - "Five genes have already been identified: calpain-3 at LGMD2A (15q15), and four members of the sarcoglycan (SG) complex, alpha-SG at LGMD2D (17q21), beta-SG at LGMD2E (4q12), gamma-SG at LGMD2C (13q12), and delta-SG at LGMD2F (5q33-q34). "
7.	Complementary DNA (cDNA)IBA 08/01/2008 - "cDNA analyses of CAPN3 enhance mutation detection and reveal a low prevalence of LGMD2A patients in Denmark." 04/01/2007 - "To elucidate the fundamental molecular changes that may be responsible for the pathological features of LGMD2A, we employed cDNA microarray analysis. " 08/01/2008 - "The present study demonstrates the value of cDNA analysis for CAPN3 in LGMD2A patients and indicates that calpainopathy is an uncommon cause of LGMD in the Denmark." 12/13/2019 - "When plasmids encoding the human calpain3 or dysferlin cDNA sequences were injected into quadriceps muscles of LGMD2A and LGMD2B mouse models, respectively, in 3-month studies, robust levels of calpain3 and dysferlin proteins were detected. " 04/01/2011 - "RT-PCR (reverse transcription-PCR) performed on total RNA from a LGMD2A patient's muscle biopsy showed complete retention of intron 12 in CAPN3 cDNA, generating a PTC (premature termination codon) that potentially elicits degradation of the nonsense mRNA by NMD (nonsense-mediated mRNA decay). "
8.	Peptide Hydrolases (Proteases)FDA Link 08/23/2013 - "Multiple muscle cell functions have been reported for CAPN3, and mutations in this protease cause limb-girdle muscular dystrophy type 2A. " 08/01/2010 - "Furthermore, our data provide direct evidence that loss of p94 protease activity can result in LGMD2A and molecular insight into how this could occur." 11/01/2009 - "Limb-girdle muscular dystrophy type 2A is an autosomal recessive disorder generated by inactivating mutations in the gene coding for the muscle specific protease calpain-3. " 09/01/2007 - "The function and normal regulation of calpain-3, a muscle-specific Ca(2+)-dependent protease, is uncertain, although its absence leads to limb-girdle muscular dystrophy type 2A. " 06/01/1999 - "We previously demonstrated that this protease is altered in limb girdle muscular dystrophy type 2A patients. "
9.	Messenger RNA (mRNA)IBA 07/01/2008 - "In the present work, we have characterised CAPN3 messenger RNA (mRNA) expression in peripheral blood, and we have performed a retrospective diagnostic study with 26 LGMD2A patients, sequencing a transcript of CAPN3 present in white blood cells (WBCs). " 02/01/2012 - "We also demonstrated variable mRNA alternative splicing among tissues and between LGMD2A patients. " 09/01/2010 - "Muscle mRNA from 15 calpainopathy patients was analyzed by RT-PCR and splicing-specific-PCR tests. " 04/01/2007 - "After comparing the gene expression profiles of the two groups of LGMD2A muscles with control muscles, we identified 29 genes whose mRNA expression profiles were specifically altered in muscles with lobulated fibers. " 10/01/2004 - "Mutations in Czech LGMD2A patients revealed by analysis of calpain3 mRNA and their phenotypic outcome."
10.	DNA (Deoxyribonucleic Acid)IBA 07/01/1997 - "DNA studies of limb-girdle muscular dystrophy type 2A in the Amish exclude a modifying mitochondrial gene and show no evidence for a modifying nuclear gene." 01/01/2017 - "In addition, DNA from 401 randomly selected unaffected villagers was analyzed to establish the carrier frequency of the LGMD2 causal mutation. " 02/01/2007 - "Our results illustrate the importance of DNA analysis for reliable establishment of mutation status, and provide a new insight into the process of mRNA decay in cells of LGMD2A patients." 11/01/1992 - "Internal DNA polymorphisms of the LD locus were analyzed in LGMD2 and CEPH families. " 02/01/2007 - "We performed analysis of the CAPN3 gene in LGMD2A patients at both the mRNA level using reverse transcription-PCR, and at the DNA level using PCR and denaturing high performance liquid chromatography. "

Therapies and Procedures

1.	Bone Marrow Transplantation (Transplantation, Bone Marrow) 01/01/2020 - "Case Report: Calpainopathy Presenting After Bone Marrow Transplantation, With Studies of Donor Genetic Content in Various Tissue Types."
2.	Therapeutics 12/04/2019 - "To test the feasibility of an autologous induced pluripotent stem cell (iPSC)-based therapy for LGMD2A, here we applied CRISPR-Cas9-mediated genome editing to iPSCs from three LGMD2A patients to enable correction of mutations in the CAPN3 gene. " 03/01/2022 - "An adolescent child referred for proximal myopathy in view of paternal history of LGMD2 but found to have signs of systemic sclerosis with overlap myositis with excellent recovery on therapy. " 07/15/2012 - "Thus, impaired CaMKII signaling and, as a result, a weakened muscle adaptation response identify a novel mechanism that may underlie LGMD2A and suggest a pharmacological target that should be explored for therapy." 12/25/2000 - "To better understand the function of calpain 3 and the pathophysiological mechanisms of LGMD2A and also to develop an adequate model for therapy research, we generated capn3-deficient mice by gene targeting. "
3.	Cell- and Tissue-Based Therapy (Cell Therapy) 12/04/2019 - "Thus, we provide here proof of concept for the integration of genome editing and iPSC technologies to develop a novel autologous cell therapy for LGMD2A." 12/04/2019 - "Gene Correction of LGMD2A Patient-Specific iPSCs for the Development of Targeted Autologous Cell Therapy."
4.	Abdominoplasty 05/01/2021 - "We report the anesthetic management with combined spinal-epidural in a patient with limb-girdle muscular dystrophy type 2A, submitted to abdominoplasty and liposuction. "
5.	Resistance Training 02/01/2013 - "Our findings suggest that supervised resistance training may be considered in the management of patients with LGMD2 and BMD."