Wikipedia

Limb–girdle muscular dystrophy

Limb–girdle muscular dystrophy (LGMD) is a genetically heterogeneous group of rare muscular dystrophies that share a set of clinical characteristics.[7] It is characterised by progressive muscle wasting which affects predominantly hip and shoulder muscles.[8] LGMD usually has an autosomal pattern of inheritance. It currently has no known cure or treatment.[3][9]

Limb–girdle muscular dystrophy
Other namesErb's muscular dystrophy[1]
Protein MYOT (also known as TTID one of the many genes whose mutations are responsible for this condition)
SpecialtyNeurology, neuromuscular medicine
SymptomsPelvic muscle weakness[2]
DurationLifelong
Types32 types[3]
CausesGenetic mutations
Diagnostic methodGenetic testing, and possibly muscle biopsy[4]
Differential diagnosisMuscular dystrophies: Duchenne, Becker, facioscapulohumeral, Emery-Dreifuss; Pompe disease; congenital myasthenic syndrome; motor neuropathy
TreatmentOccupational Therapy,speech Therapy and physical therapy[5]
Frequency2.27–10 per 100,000[6]

LGMD may be triggered or worsened in genetically susceptible individuals by statins, because of their effects on HMG-CoA reductase.[10]

Signs and symptoms

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By definition, all limb girdle muscular dystrophies (LGMD) cause progressive proximal weakness,[3] meaning weakness of the muscles on or close to the torso that worsens over time. Explicitly, LGMD preferentially affects muscles of the hip girdle, thigh, shoulder girdle, and/or upper arm.[8][6] The muscle weakness is generally symmetric.[11] Usually, the hip girdle is the first area to exhibit weakness,[2] manifesting as difficulty walking, going up and/or down stairs, rising from a chair, bending at the waist, or squatting. Because of these difficulties, falling can occur frequently. Weakness of the shoulder girdle can make lifting objects, or even elevating the arms, difficult or impossible. Rate of progression varies between patients. Eventually, the abilities to run and walk can deteriorate.[2][4] The disease commonly leads to dependence on a wheelchair within years of symptom onset, although some patients maintain mobility.[12][2] Eventually the disease can affect other muscles such as the ones located in the face.

By definition, LGMDs primarily affect skeletal muscles,[3] although cardiac muscle can be affected to a lesser degree in select subtypes, which can cause palpitations.

There can be significant variability in disease features and severity between LGMD subtypes, and even within any given LGMD subtype.[11] Additional possible presentations include:

 
PVC (a type of palpitation) recording
An audio clip recording of a PVC symptom, made with a cardiac event monitor
Problems playing this file? See media help.

Genetics

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The various molecules involved in muscle function and implicated in LGMD

LGMD is a genetic and heritable disorder, due to one of many genetic mutations of proteins involved in muscle function. All currently identified LGMDs have an inheritance pattern that is dominant or recessive, although the definition of LGMD allows for diseases with more complicated inheritance patterns to be classified as LGMD. Pathogenic mutations are mostly in coding regions, but non-coding causative variants were also reported.[14]

In Euroasia CAPN3 mutations are the most common cause of LGMD,[15] however in northern Europe mutations in FKRP are also very common.[16] HMG CoA Reductase homozygous mutation leads to a form of LGMD that may respond to treatment with the downstream metabolite mevalonolactone in the cholesterol synthesis pathway.[17]

Diagnosis

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The diagnosis of limb–girdle muscular dystrophy can be done via muscle biopsy, which will show the presence of muscular dystrophy, and genetic testing is used to determine which type of muscular dystrophy a patient has. Immunohistochemical dystrophin tests can indicate a decrease in dystrophin detected in sarcoglycanopathies. In terms of sarcoglycan deficiency there can be variance (if α-sarcoglycan and γ-sarcoglycan are not present then there's a mutation in LGMD2D).[4]

The 2014 Evidence-based guideline summary: Diagnosis and treatment of limb–girdle and distal dystrophies indicates that individuals suspected of having the inherited disorder should have genetic testing. Other tests/analysis are:[4][5]

  • High CK levels (10–150 times normal)
  • MRI can indicate different types of LGMD.
  • EMG can confirm the myopathic characteristic of the disease.
  • Electrocardiography (cardiac arrhythmias in LGMD1B can occur)

Types

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The "LGMD D" family is autosomal dominant, and the "LGMD R" family is autosomal recessive.[3] Limb–girdle muscular dystrophy is explained in terms of gene, locus, OMIM and type as follows:

LGMD subtypes
Name[3] Inheritance Old Name[12] OMIM Gene Gene also implicated in: Notes
LGMD D1 DNAJB6-related Autosomal dominant LGMD1D & LGMD1E 603511 DNAJB6
LGMD D2 TNP03-related LGMD1F 608423 TNPO3
LGMD D3 HNRNPDL-related LGMD1G 609115 HNRPDL
LGMD D4 calpain3-related LGMD1I 618129 CAPN3 LGMD R1 Also referred to as "autosomal dominant calpainopathy."
LGMD D5

collagen 6-related

Bethlem myopathy 1 158810 COL6A1, COL6A2, COL6A3 Bethlem myopathy 1 (recessive), LGMD R22; Ullrich congenital muscular dystrophy 1
? Bethlem myopathy 2 616471 COL12A1 Ullrich congenital muscular dystrophy 2 Formerly referred to as "Ehlers–Danlos syndrome, myopathic type"
LGMD R1 calpain3-related Autosomal recessive LGMD2A 253600 CAPN3 LGMD D4 Also referred to as "autosomal recessive calpainopathy."[18]
LGMD R2 dysferlin-related LGMD2B 253601 DYSF Miyoshi myopathy type 1 (MMD1 - 254130).[19] A dysferlinopathy
LGMD R3 α-sarcoglycan-related LGMD2D 608099 SGCA sarcoglycanopathies
LGMD R4 β -sarcoglycan-related LGMD2E 604286 SGCB
LGMD R5 γ -sarcoglycan-related LGMD2C 253700 SGCG
LGMD R6 δ-sarcoglycan-related LGMD2F 601287 SGCD
LGMD R7 telethonin-related LGMD2G 601954 TCAP
LGMD R8 TRIM 32-related LGMD2H 254110 TRIM32
LGMD R9 FKRP-related LGMD2I 607155 FKRP Congenital muscular dystrophy An α-dystroglycanopathy
LGMD R10 titin-related LGMD2J 608807 TTN Congenital myopathy
LGMD R11 POMT1-related LGMD2K 609308 POMT1 Congenital muscular dystrophy An α-dystroglycanopathy
LGMD R12 anoctamin5-related LGMD2L 611307 ANO5 Miyoshi myopathy type 3 (MMD3 - 613319)
LGMD R13 Fukutin-related LGMD2M 611588 FKTN Congenital muscular dystrophy An α-dystroglycanopathy
LGMD R14 POMT2-related LGMD2N 607439 POMT2 Congenital muscular dystrophy An α-dystroglycanopathy
LGMD R15 POMGnT1-related LGMD2O 606822 POMGNT1 Congenital muscular dystrophy An α-dystroglycanopathy
LGMD R16 α-dystroglycan-related LGMD2P 613818 DAG1 Congenital muscular dystrophy An α-dystroglycanopathy
LGMD R17 plectin-related LGMD2Q 613723 PLEC1
LGMD R18 TRAPPC11-related LGMD2S 615356 TRAPPC11
LGMD R19 GMPPB-related LGMD2T 615352 GMPPB Congenital muscular dystrophy An α-dystroglycanopathy
LGMD R20 ISPD-related LGMD2U 616052 ISPD Congenital muscular dystrophy An α-dystroglycanopathy
LGMD R21 POGLUT1-related LGMD2Z 617232 POGLUT1
LGMD R22 collagen 6-related Bethlem myopathy 1 158810 COL6A1, COL6A2, COL6A3 Ullrich congenital muscular dystrophy 1; LGMD D5; Congenital myosclerosis (COL6A2)
LGMD R23 laminin α2-related Laminin α2-related muscular dystrophy 156225 LAMA2 Congenital muscular dystrophy
LGMD R24 POMGNT2-related POMGNT2-related muscular dystrophy 618135 POMGNT2 Congenital muscular dystrophy An α-dystroglycanopathy
LGMD R25[7] LGMD2X 616812 BVES
LGMD R26[20] n/a 618848 POPDC3
LGMD R27[21] n/a 619566 JAG2
LGMD R28[22] Myopathy, limb–girdle, adult-onset (MYPLG) 620375 HMGCR
LGMD R(number pending)[7] Myofibrillar myopathy 8 (MFM8) 617258 PYROXD1 Adult-onset Limb–girdle phenotype[23]

LGMD criteria

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For a disease entity to be classified as an LGMD, the following criteria must be met:[3]

  • genetic, with an identifiable inheritance pattern such as autosomal dominant, autosomal recessive, digenic, or polygenic.
  • relatively selective to skeletal muscle
  • predominantly proximal muscle involvement
  • independent walking is achieved at one point in life
  • elevated serum creatine kinase
  • muscle fiber loss
  • dystrophic changes in muscle histology
  • degenerative changes on medical imaging
  • end-stage pathology seen in the most affected muscles
  • described in at least two unrelated families

Differential

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Many diseases can manifest similarly to LGMD.[6] Dystrophinopathies, including Duchenne muscular dystrophy, Becker muscular dystrophy, and manifesting dystrophinopathy in female carriers, can present similarly to LGMD.[6] Facioscapulohumeral muscular dystrophy can appear similarly, especially when it spares the facial muscles.[6] Also in the differential are Emery–Dreifuss muscular dystrophies, Pompe disease, later-onset congenital myasthenic syndromes, and proximal-predominant hereditary motor neuropathies.[6]

Treatment

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Cardiac muscle

There are few studies corroborating the effectiveness of exercise for limb–girdle muscular dystrophy. However studies have shown that exercise can, in fact, damage muscles permanently due to intense muscle contraction.[24] Physical therapy may be required to maintain as much muscle strength and joint flexibility as possible. Calipers may be used to maintain mobility and quality of life. Careful attention to lung and heart health is required, corticosteroids in LGMD 2C-F individuals, shows some improvement.[13] Additionally individuals can follow management that follows:[5]

The sarcoglycanopathies could be possibly amenable to gene therapy.[25]

Prognosis

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In terms of the prognosis of limb–girdle muscular dystrophy in its mildest form, affected individuals have near-normal muscle strength and function. LGMD isn't typically a fatal disease, though it may eventually weaken the heart and respiratory muscles, leading to illness or death due to secondary disorders.

Epidemiology

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The minimum prevalence of limb–girdle muscular dystrophy, as a group, likely ranges 2.27–10 per 100,000 (1:44,000 to 1:10,000).[6] LGMD is the fourth most common muscular dystrophy, after the dystrophinopathies, myotonic dystrophies, and facioscapulohumeral muscular dystrophy.[26] The prevalence of individual LGMDs, as studied in the United States, in descending order, are those due to mutation of 1) calpain, 2) dysferlin, 3) collagen VI, 4) sarcoglycans, 5) anoctamin 5, and 6) fukutin-related protein.[6] In Euroasia CAPN3 mutations are the most common cause of LGMD, however in northern Europe mutations in FKRP are also very common.[15] It is difficult to calculate the worldwide prevalence of even the most common LGMD types, due to the founder effect causing varying prevalence by region.[7] The less common types are very rare, often only described is limited regions of the world.[7]

History

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The term 'limb girdle muscular dystrophy' was published in 1954, describing a group of heterogeneous conditions that clinicians noticed to be distinct from Duchenne muscular dystrophy, facioscapulohumeral muscular dystrophy, and myotonic dystrophy.[3] The genetics of LGMDs began to be understood in the late 1900s, which led the European Neuromuscular Centre (ENMC) to establish a consensus on classification of LGMDs in 1995.[3] The classification scheme at that time denoted autosomal dominant LGMDs as 'LGMD1' and autosomal recessive LGMDs as 'LGMD2.'[3] A letter was appended to the names of LGMDs according to the order of discovery of the causal genetic mutation.[3] As LGMD2Z was established, the question arose of what letter to assign the next discovered LGMD2.[3] With this issue, among other motives, the ENMC established a new consensus on the classification and definition of LGMD in 2017.[3] With the new definition, several diseases were removed from the LGMD category:

Diseases previously classified as LGMD until the 2017 consensus on LGMD criteria[3]
Current name Old Name OMIM Gene Locus Reason for exclusion
Myofibrillar myopathy 3 (MFM3) LGMD1A 609200 MYOT Distal weakness
Emery–Dreifuss muscular dystrophy 2, autosomal dominant (EDMD2) LGMD1B 181350 LMNA EDMD phenotype and significant cardiac involvement
Rippling muscle disease 2 LGMD1C 606072 CAV3 Mainly characterized by muscle rippling and pain
Myofibrillar myopathy 1 (MFM1) LGMD1D & LGMD2R 601419 DES Distal weakness and significant cardiac involvement
Not yet given new nomenclature LGMD1H 613530 unknown 3p23–p25.1 "False linkage"[3] Possibly mitochondrial myopathy[27]
Pompe disease (Glycogen storage disease type 2) LGMD2V 232300 GAA Known disease entity, histological changes
Muscular dystrophy, autosomal recessive, with cardiomyopathy and triangular tongue (MDRCMTT) LGMD2W 616827 LIMS2 One known family
Muscular dystrophy, autosomal recessive, with rigid spine and distal joint contractures (MRRSDC) LGMD2Y 617072 TOR1AIP1 One known family

Research

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alpha sarcoglycan Left side-normal muscle /right side LGMD2

There is a variety of research under way targeted at various forms of limb–girdle muscular dystrophy. Among the treatments thought to hold promise is gene therapy, which is the delivery of genetic material, often a copy of a healthy gene, into cells.[28]

According to a review by Bengtsson et al. some success with AAV-mediated gene therapies (for different disorders) have increased interest in researchers, with CRISPR/Cas9 and exon-skipping helping these therapeutic goals along[29]. Limb–girdle muscular dystrophies have many different types which are due to different gene mutations. LGMD2D is caused by a mutation in the α-sarcoglycan gene. Future treatment could be had by gene therapy through recombinant adeno-associated vectors.[30]

According to a review by Straub, et al., there are several research issues that need to be addressed: the rareness of the disease, poor understanding of the mechanism of LGMD R, and absence of patient cohorts, all contributing to lack of biomarkers for LGMD. The review goes on to state that animal models for LGMD R have been used to analyze therapeutic medications. Also, although prednisone has been used and has had positive effects on affected LGMD2 individuals, there is still no evidence of its effectiveness in trials that are placebo-controlled.[31]

See also

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References

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  1. ^ Newfoundland, FRCP William Pryse-Phillips MD, FRCP(C) Faculty of Medicine Health Sciences Centre Memorial University of Newfoundland St John's (2009-05-06). Companion to Clinical Neurology. Oxford University Press, USA. p. 579. ISBN 9780199710041.{{cite book}}: CS1 maint: multiple names: authors list (link)
  2. ^ a b c d e f MedlinePlus Encyclopedia: Limb-girdle muscular dystrophies
  3. ^ a b c d e f g h i j k l m n o Straub, V; Murphy, A; Udd, B; LGMD workshop study, group. (August 2018). "229th ENMC international workshop: Limb girdle muscular dystrophies - Nomenclature and reformed classification Naarden, the Netherlands, 17-19 March 2017". Neuromuscular Disorders. 28 (8): 702–710. doi:10.1016/j.nmd.2018.05.007. PMID 30055862. S2CID 51865029.
  4. ^ a b c d "Limb-Girdle Muscular Dystrophy: Practice Essentials, Background, Pathophysiology". eMedicine. 27 September 2023. Retrieved 4 January 2024.
  5. ^ a b c Narayanaswami, Pushpa; Weiss, Michael; Selcen, Duygu; David, William; Raynor, Elizabeth; Carter, Gregory; Wicklund, Matthew; Barohn, Richard J.; Ensrud, Erik (2014-10-14). "Evidence-based guideline summary: Diagnosis and treatment of limb-girdle and distal dystrophies". Neurology. 83 (16): 1453–1463. doi:10.1212/WNL.0000000000000892. ISSN 0028-3878. PMC 4206155. PMID 25313375.
  6. ^ a b c d e f g h Wicklund, MP (December 2019). "The Limb-Girdle Muscular Dystrophies". Continuum (Minneapolis, Minn.). 25 (6): 1599–1618. doi:10.1212/CON.0000000000000809. PMID 31794462. S2CID 208531741.
  7. ^ a b c d e f Barton, ER; Pacak, CA; Stoppel, WL; Kang, PB (29 July 2020). "The ties that bind: functional clusters in limb-girdle muscular dystrophy". Skeletal Muscle. 10 (1): 22. doi:10.1186/s13395-020-00240-7. PMC 7389686. PMID 32727611.
  8. ^ a b "Limb-girdle muscular dystrophy".
  9. ^ Pozsgai, E; Griffin, D; Potter, R; Sahenk, Z; Lehman, K; Rodino-Klapac, LR; Mendell, JR (October 2021). "Unmet needs and evolving treatment for limb girdle muscular dystrophies". Neurodegenerative Disease Management. 11 (5): 411–429. doi:10.2217/nmt-2020-0066. PMID 34472379. S2CID 237389009.
  10. ^ Morales-Rosado JA, Schwab TL, et al. (2023-06-01). "Bi-allelic variants in HMGCR cause an autosomal-recessive progressive limb-girdle muscular dystrophy". American Journal of Human Genetics. 110 (6): 989–997. doi:10.1016/j.ajhg.2023.04.006. PMC 10257193. PMID 37167966.
  11. ^ a b Murphy, AP; Straub, V (22 July 2015). "The Classification, Natural History and Treatment of the Limb Girdle Muscular Dystrophies". Journal of Neuromuscular Diseases. 2 (s2): S7–S19. doi:10.3233/JND-150105. PMC 5271430. PMID 27858764.
  12. ^ a b Pegoraro, Elena; Hoffman, Eric P. (1993-01-01). "Limb-Girdle Muscular Dystrophy Overview – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY". In Pagon, Roberta A.; Adam, Margaret P.; Ardinger, Holly H.; Wallace, Stephanie E.; Amemiya, Anne; Bean, Lora JH; Bird, Thomas D.; Fong, Chin-To; Mefford, Heather C. (eds.). Limb-Girdle Muscular Dystrophy Overview. Seattle (WA): University of Washington, Seattle. PMID 20301582.update 2012
  13. ^ a b c d "Limb-girdle Muscular Dystrophy | Doctor". 22 June 2023.
  14. ^ Macias, Anna; Fichna, Jakub Piotr; Topolewska, Malgorzata; Rȩdowicz, Maria J.; Kaminska, Anna M.; Kostera-Pruszczyk, Anna (2021). "Targeted Next-Generation Sequencing Reveals Mutations in Non-coding Regions and Potential Regulatory Sequences of Calpain-3 Gene in Polish Limb-Girdle Muscular Dystrophy Patients". Frontiers in Neuroscience. 15: 692482. doi:10.3389/fnins.2021.692482. ISSN 1662-4548. PMC 8551377. PMID 34720847.
  15. ^ a b Fichna JP, Macias A, Piechota M, Korostynski M, Potulska-Chromik A, Redowicz MJ, Zekanowski C (July 2018). "Whole-exome sequencing identifies novel pathogenic mutations and putative phenotype-influencing variants in Polish limb-girdle muscular dystrophy patients". Human Genomics. 12 (1): 34. doi:10.1186/s40246-018-0167-1. PMC 6029161. PMID 29970176.
  16. ^ Norwood FL, Harling C, Chinnery PF, Eagle M, Bushby K, Straub V (November 2009). "Prevalence of genetic muscle disease in Northern England: in-depth analysis of a muscle clinic population". Brain. 11 (132): 3175–3186. doi:10.1093/brain/awp236. PMC 8551377. PMID 34720847.
  17. ^ Yogev Y, Shorer Z, Koifman A, Wormser O, Drabkin M, Halperin D, Dolgin V, Proskorovski-Ohayon R, Hadar N, Davidov G, Nudelman H, Zarivach R, Shelef I, Perez Y, Birk OS (February 2023). "Limb girdle muscular disease caused by HMGCR mutation and statin myopathy treatable with mevalonolactone". Proc Natl Acad Sci U S A. 120 (7): e2217831120. Bibcode:2023PNAS..12017831Y. doi:10.1073/pnas.2217831120. PMC 9963716. PMID 36745799.
  18. ^ Lasa-Elgarresta, J; Mosqueira-Martín, L; Naldaiz-Gastesi, N; Sáenz, A; López de Munain, A; Vallejo-Illarramendi, A (13 September 2019). "Calcium Mechanisms in Limb-Girdle Muscular Dystrophy with CAPN3 Mutations". International Journal of Molecular Sciences. 20 (18): 4548. doi:10.3390/ijms20184548. PMC 6770289. PMID 31540302.
  19. ^ Aoki, Masashi (March 5, 2015). "Dysferlinopathy". GeneReviews. PMID 20301480.
  20. ^ Benarroch, Louise; Bonne, Gisèle; Rivier, François; Hamroun, Dalil (December 2020). "The 2021 version of the gene table of neuromuscular disorders (nuclear genome)" (PDF). Neuromuscular Disorders. 30 (12): 1008–1048. doi:10.1016/j.nmd.2020.11.009. PMID 33257164. S2CID 227123684.
  21. ^ Coppens, S; Barnard, AM; Puusepp, S; Pajusalu, S; Õunap, K; Vargas-Franco, D; Bruels, CC; Donkervoort, S; Pais, L; Chao, KR; Goodrich, JK; England, EM; Weisburd, B; Ganesh, VS; Gudmundsson, S; O'Donnell-Luria, A; Nigul, M; Ilves, P; Mohassel, P; Siddique, T; Milone, M; Nicolau, S; Maroofian, R; Houlden, H; Hanna, MG; Quinlivan, R; Beiraghi Toosi, M; Ghayoor Karimiani, E; Costagliola, S; Deconinck, N; Kadhim, H; Macke, E; Lanpher, BC; Klee, EW; Łusakowska, A; Kostera-Pruszczyk, A; Hahn, A; Schrank, B; Nishino, I; Ogasawara, M; El Sherif, R; Stojkovic, T; Nelson, I; Bonne, G; Cohen, E; Boland-Augé, A; Deleuze, JF; Meng, Y; Töpf, A; Vilain, C; Pacak, CA; Rivera-Zengotita, ML; Bönnemann, CG; Straub, V; Handford, PA; Draper, I; Walter, GA; Kang, PB (6 May 2021). "A form of muscular dystrophy associated with pathogenic variants in JAG2". American Journal of Human Genetics. 108 (5): 840–856. doi:10.1016/j.ajhg.2021.03.020. PMC 8206160. PMID 33861953.
  22. ^ "MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 28; LGMDR28". www.omim.org. Retrieved 2024-01-03.
  23. ^ Sainio, Markus T.; Välipakka, Salla; Rinaldi, Bruno; Lapatto, Helena; Paetau, Anders; Ojanen, Simo; Brilhante, Virginia; Jokela, Manu; Huovinen, Sanna; Auranen, Mari; Palmio, Johanna; Friant, Sylvie; Ylikallio, Emil; Udd, Bjarne; Tyynismaa, Henna (February 2019). "Recessive PYROXD1 mutations cause adult-onset limb-girdle-type muscular dystrophy". Journal of Neurology. 266 (2): 353–360. doi:10.1007/s00415-018-9137-8. ISSN 1432-1459. PMC 6373352. PMID 30515627.
  24. ^ Siciliano G, Simoncini C, Giannotti S, Zampa V, Angelini C, Ricci G (2015). "Muscle exercise in limb girdle muscular dystrophies: pitfall and advantages". Acta Myologica. 34 (1): 3–8. PMC 4478773. PMID 26155063.
  25. ^ Reference, Genetics Home. "limb-girdle muscular dystrophy". Genetics Home Reference. Retrieved 2016-04-22.
  26. ^ Bockhorst, J; Wicklund, M (August 2020). "Limb Girdle Muscular Dystrophies". Neurologic Clinics. 38 (3): 493–504. doi:10.1016/j.ncl.2020.03.009. PMID 32703463. S2CID 220730696.
  27. ^ Bisceglia, Luigi; Zoccolella, Stefano; Torraco, Alessandra; Piemontese, Maria Rosaria; Dell'Aglio, Rosa; Amati, Angela; De Bonis, Patrizia; Artuso, Lucia; Copetti, Massimiliano; Santorelli, Filippo Maria; Serlenga, Luigi; Zelante, Leopoldo; Bertini, Enrico; Petruzzella, Vittoria (June 2010). "A new locus on 3p23-p25 for an autosomal-dominant limb-girdle muscular dystrophy, LGMD1H". European Journal of Human Genetics. 18 (6): 636–641. doi:10.1038/ejhg.2009.235. ISSN 1476-5438. PMC 2987336. PMID 20068593.
  28. ^ Reference, Genetics Home. "How does gene therapy work?". Genetics Home Reference. Retrieved 2016-04-23.
  29. ^ Lee, Joshua J. A.; Maruyama, Rika; Duddy, William; Sakurai, Hidetoshi; Yokota, Toshifumi (2018-12-07). "Identification of Novel Antisense-Mediated Exon Skipping Targets in DYSF for Therapeutic Treatment of Dysferlinopathy". Molecular Therapy. Nucleic Acids. 13: 596–604. doi:10.1016/j.omtn.2018.10.004. ISSN 2162-2531. PMC 6234522. PMID 30439648.
  30. ^ Bengtsson, Niclas E.; Seto, Jane T.; Hall, John K.; Chamberlain, Jeffrey S.; Odom, Guy L. (2016-04-15). "Progress and prospects of gene therapy clinical trials for the muscular dystrophies". Human Molecular Genetics. 25 (R1): R9–R17. doi:10.1093/hmg/ddv420. ISSN 0964-6906. PMC 4802376. PMID 26450518.
  31. ^ Straub, Volker; Bertoli, Marta (February 2016). "Where do we stand in trial readiness for autosomal recessive limb girdle muscular dystrophies?". Neuromuscular Disorders. 26 (2): 111–125. doi:10.1016/j.nmd.2015.11.012. PMID 26810373.

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