Classification of Limb–Girdle Muscular Dystrophies

Version	Summary	Created by	Modification	Content Size	Created at	Operation
1		Camille Bouchard	--	2454	2023-07-26 14:12:27	\|
2	references update	Fanny Huang	Meta information modification	2454	2023-07-27 07:06:09	\|

This entry is adapted from the peer-reviewed paper 10.3390/jcm12144769

Limb–girdle muscular dystrophies (LGMDs) are caused by mutations in multiple genes. Limb–girdle muscular dystrophies (LGMD) are muscular dystrophies that affect skeletal muscles, mostly proximal (hips and shoulder muscles). They are caused by a mutation in a gene encoding a protein, which is specific to each subtype. LGMD inheritance is autosomal.

limb–girdle muscular dystrophy LGMD classification

1. Introduction

Limb–girdle muscular dystrophies (LGMD) are muscular dystrophies that affect skeletal muscles, mostly proximal (hips and shoulder muscles). They are caused by a mutation in a gene encoding a protein, which is specific to each subtype. LGMD inheritance is autosomal. This is in contrast to Duchenne or Becker muscular dystrophies, which are caused by a mutation in the DMD gene located on the X chromosome ^[1]. Some LGMD forms are dominant, and others are recessive.

2. Classification of Limb–Girdle Muscular Dystrophies

2.1. Autosomal Dominant

For example, LGMD 1A is characterized by a mutation in the MYOT gene, responsible for myotilin synthesis ^[2]^[3] which cross-links actin filaments and controls sarcomere assembly ^[4]. However, this disease is not included in the new classification by Straub et al. (2018) because the weakness is distal and does not affect proximal muscles ^[5]. In fact, the most frequent phenotype is a late-onset distal myopathy affecting ankles, feet or calves ^[6]. Cases of respiratory insufficiency or cardiac failure are also reported ^[7].

LGMD 1B is caused by mutations in the LMNA gene coding for Lamin A/C ^[8]. This in turn causes alterations in the nuclear envelope in fibroblasts ^[9]. Straub et al. (2018) do not consider this myopathy as an LGMD because it is associated with cardiac arrhythmia ^[5]. It is therefore not included in the new nomenclature since the main effect is not exerted on proximal muscles.

LGMD 1C occurs due to mutations in the CAV3 gene ^[10], causing a caveolin-3 deficiency associated with skeletal muscle weakness due to impaired mitochondrial form and function ^[11]. This pathology was excluded from the new classification due to the muscle rippling and myalgia ^[5]. A recent Korean study showed that the phenotype is variable, being mild for some patients and more severe for others. HyperCKemia is found in all patients, whereas myopathic features are less frequent and can occur as ankle contracture, calf hypertrophy, exercise intolerance, or muscular cramps ^[12].

LGMD 1D (now LGMD D1) is characterized by a mutation in the DNAJB6 gene, which encodes for a co-chaperone protein implicated in sarcomeric protein maintenance and aggregation ^[13]. Patient muscle magnetic resonance imaging (MRI) shows fat infiltration, and biopsies show an increased number of internal nuclei and rimmed vacuoles ^[14]. The affected muscles are both proximal and distal; the lower and proximal limbs are affected most severely, while the effects are mild in the distal and upper ones.

LGMD 1E occurs due to mutations in the DES gene encoding for desmin ^[15]. A mutation in this protein can lead to desmin aggregate formation and/or to the development of an irregular muscle fibre shape ^[16]. LGMDs are not considered in the new classification because of distal weakness and cardiomyopathy ^[5]. Desminopathy shows fatty replacement in semitendinosus, gastrocnemius and soleus MRI. The typical phenotype is characterized by distal weakness, but facial and bulbar weakness were also reported ^[17]

LGMD 1F (now LGMD D2) is associated with mutations in the TNPO3 gene coding for transportin 3 ^[18]. This protein function is still being studied, but abnormalities in sarcomeric assembly have been observed via patient biopsies ^[19]. The age of onset and severity of phenotype have a high variability. Typically, however, a pelvic lower girdle weakness is noticed first, followed by the atrophy of the axial muscle and shoulder girdle. MRI also shows fatty replacement of fibres in pelvic and thigh muscles. Biopsy results show rimmed vacuoles and enlarged nuclei ^[20].

LGMD 1G (now LGMD D3) is caused by a defect in the heterogenous nuclear ribonucleoprotein D-like (hnRNPDL) protein ^[21] and patient muscles show rimmed vacuoles ^[22]. The protein has been shown to regulate transcription and alternative splicing ^[23].

LGMD 1H is another autosomal dominant type of LGMD with an alteration in a gene situated in chromosome 3 (3p23–p25). However, it remains unassociated with a specific protein ^[24] and therefore cannot be classified as an LGMD since all the characteristics one are not fulfilled ^[5].

LGMD 1I (now LGMD D4) is caused by dominant mutations in the CAPN3 gene, encoding for calpain 3. Research shows that missense mutations lead to a milder phenotype and null mutations to increased phenotype severity ^[25]. Fat infiltration int the affected muscles (thigh adductors and semimembranosus, but also calf gastrocnemius and soleus) is also noticed in MRI and happens before the deterioration of muscle function ^[26].

Bethlem myopathy (now LGMD D5) is now also classified as an LGMD and can be caused by a dominant mutation in COL6A1, COL6A2 or COL6A3 genes, encoding for the Collagen 6 protein that plays a role in extracellular matrix structure and muscle regeneration ^[5]. This myopathy also causes there to be a higher fat fraction in the muscles, especially in the psoas major ^[27], and recent authors have suggested that this be used as an MRI diagnosis tool. Other MRI patterns also indicate this pathology, such as a “target sign” located in the rectus femoris or a “sandwich sign” in the vastus lateralis ^[28].

2.2. Autosomal Recessive

As for autosomal recessive limb–girdle muscular dystrophies, LGMD 2A (now LGMD R1) is caused by recessive mutations in CAPN3, a gene encoding for calpain 3 ^[29], which could regulate the sarcomere ^[30]. The dominant form is also described above as LGMD 1I/D4.

LGMD 2B (LGMD R2) is associated with mutations in the DYSF gene that impairthe synthesis of dysferlin, a protein responsible for sarcomere stability and muscular repair ^[31]. The posterior thigh and leg muscles are the most affected areas and show a progressive fat fraction increase, which is accentuated when patients become non-ambulant ^[32]. Two-thirds of patients have a diamond-shaped bulge on their quadriceps when in action ^[33].

LGMD 2C (LGMD R5) is caused by mutations in the SGCG gene, which synthetizes the γ-Sarcoglycan protein. This protein is part of the DAP complex and plays a role in the cytoskeleton extracellular matrix link ^[34]. The phenotype severity varies in siblings with the same mutation and is not related to the age of onset ^[35]. The phonotype is considered severe when patients lose ambulation before 13 years of age.

LGMD 2D (LGMD R3) is also caused by a mutation in a gene of the sarcoglycan complex: the SGCA gene responsible for the synthesis of the α-Sarcoglycan protein. The main signs include pelvic girdle weakness, fatty replacement, and atrophy of the vastus intermedius, semimembranosus and biceps femoris muscles ^[36].

LGMD 2E (LGMD R4) is associated with a mutation in the SGCB gene, related to the β-Sarcoglycan protein. The phenotype is a weakness and fatty replacement in: Latissimus dorsi, spine extensors, abdominal belt, glutei, adductors, and various thigh muscles ^[37].

LGMD 2F (LGMD R6) is caused by a mutation in the SGCD gene coding for the δ-Sarcoglycan protein. The phenotype is variable, but generally involves a progressive atrophy of proximal muscles and high serum creatine kinase. Some patients also present cardiomyopathy ^[38].

LGMD 2G (LGMD R7) is related to mutations in the TCAP gene encoding for telethonin, which plays a role in myofibrillogenesis in interaction with titin in the sarcomeric Z-disk ^[39]^[40]. The first sign of this is generally thigh muscle weakness progressively also affecting calf muscles via fatty infiltration in the glutei, hip and thigh muscles ^[41].

LGMD 2H (LGMD R8) is known for mutations in the TRIM32 gene, which codes for the tripartite motif-containing protein 32 responsible for the movement of Ca²⁺ in skeletal muscles ^[42]. Patients present calf hypertrophy and weakness. Their muscles contain fibres of various size, small vacuoles, and increased numbers of internal nuclei ^[43].

LGMD 2I (LGMD R9) is caused by mutations in the FKRP gene, coding for fukutin-related protein. This protein is necessary for the glycosylation of α-dystroglycan ^[44]. Muscle biopsies show different fibre modifications: some are hypertrophic, while others are split, hyaline, rounded or necrotic ^[45].

LGMD 2J (LGMD R10) is caused by mutations in the TTN gene. This codes for titin, a protein responsible for muscle tension ^[46]. Patients have weakened thighs and their muscle biopsy shows rimmed vacuoles containing amyloid accumulation ^[47].

LGMD 2K (LGMD R11) and LGMD 2N (LGMD R14) are due to mutations in the POMT1 and POMT2 genes, respectively. These genes allow for the synthesis of protein O-mannosyltransferase 1 and 2, of which co-expression is necessary for O-mannosylation, an important reaction in α-dystroglycan ^[48]. LGMD 2J (LGMD R10) shows proximal limbs weakness and cognitive impairment ^[49].

LGMD 2L (LGMD R12) is associated with mutations in the ANO5 gene, which encodes for the Anoctamin 5 protein necessary for achieving functional calcium-activated chloride channels in the muscles ^[50]. The phenotype is one of prominent asymmetrical quadriceps femoris and biceps brachii atrophy ^[50].

LGMD 2M (LGMD R13) is linked to a mutation in the FKTN gene. The fukutin protein also plays a role in the glycosylation of α-dystroglycan ^[51]. This LGMD causes proximal muscle weakness in early childhood, with the occurrence of hypotonia and/or hypertrophy. Some patients have ocular problems, cognitive impairment or cardiomyopathy ^[52].

LGMD 2N (LGMD R14) is caused by a mutation in the POMT2 gene necessary for the synthesis of protein O-mannosyltransferase 2. The phenotype is generally responsible for walking difficulties and pain during exercise. Hamstrings, paraspinal and gluteal muscles are the first parts of the body affected, leading to a strength reduction in hips as well as knee flexors and extensors. Cognitive impairment is also reported ^[53].

LGMD 2O (LGMD R15) is caused by mutations in the POMGnT1 gene, which codes for protein O-mannose beta-1,2-Nacetylglucosaminyltranserase 1. Former POMGNT2-related muscular dystrophy (LGMD R24) was also called Walker–Warburg syndrome or muscle–eye–brain disease and is now categorized as an LGMD since it corresponds to all LGMD new criteria. It is caused by a mutation in the POMGnT2 gene, encoding for protein O-mannose beta-1,2-Nacetylglucosaminyltranserase 2. Both protein O-mannose beta-1,2-Nacetylglucosaminyltranserase 1 and 2 catalyse a modification of α-dystroglycan ^[54]. POMGnT1 is necessary for the synthesis of the M1 core glycan structure. MGAT5B is then added to form the M2 core, and the addition of POMGnT2 then transforms it into the M3 core ^[54]. LGMD 2O (LGMD R15) patients have proximal limb muscle weakness around puberty. The affected muscles are calves, quadriceps, hamstrings and deltoids. Myopia is also reported among patients ^[55].

LGMD 2P (LGMD R16) occurs due to mutations in the DAG1 gene, encoding for dystroglycan, a protein that is part of the dystroglycan complex ^[56]. In this case, a proximal muscle weakness is reported along with cognitive impairment ^[57].

LGMD 2Q (LGMD R17) occurs when there is a mutation in the PLEC1 gene. This gene encodes for the synthesis of the plectin protein. This has many roles, including cell survival, cell growth, actin organization and T-cell activation ^[56]. Progressive limb muscle weakness is reported in deltoids, erector spinae, glutei, biceps femoris and adductor magnus. Some plectinopathies include skin affectation, but case studies do not include skin problems ^[58].

LGMD 2R is not classified as an LGMD any longer, and this is caused by a mutation in the DES gene encoding for desmin. Its role is to connect sarcomeres together in order to form myofibrils ^[56]. It was rejected from the LGMD category since the weakness it induces is distal, not proximal ^[5].

LGMD 2S (LGMD R18) occurs due to mutations in TRAPPC11. This encodes for transport protein particle complex 11, which is responsible for the transport between endoplasmic reticulum and Golgi apparatus ^[56]. The onset occurs during school age and the proximal muscle weakness is progressive. The hips are more affected than shoulders and the development of a respiratory restrictive disorder is reported in some patients ^[59].

LGMD 2T (LGMD R19) is associated with the GMPPB gene, encoding for the GDP-mannose pyrophosphorylase B protein. Its function is to produce GDP-mannose for the O-mannosylation of α-dystroglycan ^[60]. Paraspinal and hamstring muscles are the most affected by this, as seen per MRI, and the phenotype can cause hypotonia, epilepsy, cognitive impairment, cataracts and cardiomyopathy ^[61].

LGMD2U (LGMDR20) is related to mutations in the ISPD gene. Its protein is isoprenoid synthase, responsible for glycosylation of α-dystroglycan ^[62]. The phenotype includes sural hypertrophy and moderate proximal weakness ^[63].

LGMD2V is associated with mutations in the GAA gene. This encodes for α-1,4-Glucosidase, an important protein for lysozyme function ^[56]. It is not categorized as an LGMD and is now called Pompe disease ^[64]. The phenotype varies from mild to severe, its effects include a progressive proximal muscle weakness, and it can also involve the respiratory or cardiac muscles ^[65].

LGMD2W is caused by mutations in the LIMS2 gene, which synthetizes Lim and senescent cell antigen-like domains 2 protein. This protein is involved in cell spreading and migration ^[56]. It was only reported in one family and, therefore, cannot be considered an LGMD yet. This is because Straub et al. (2018) consider it an LGMD only when 2 or more unrelated families have the same pathology ^[5]. The patients develop and early onset proximal weakness. This includes calf hypertrophy, leading to severe quadriparesis during adolescence. A dilated cardiomyopathy was also reported in both patients ^[66].

LGMD2X is related to the BVES gene for blood vessel endocardial substance. This encodes for Popeye domain-containing protein 1 (POPDC1) that is involved in the structure and function of cardiac and skeletal muscle cells ^[56]. This myopathy was recently reported in 5 more families, making it part of the LGMDs ^[5]. An article from May 2022 classifies LGMD2X as LGMDR25 (OMIM 616812) ^[67]. The reported symptoms are exercise-induced myalgia of the thighs and hips, as well as cardiac arrhythmia.

LGMD2Y is associated with mutations in the TOR1A1P1 gene, known for the Torsin 1A-interacting protein 1. This protein serves as a link between the nuclear membrane and lamina during cell division ^[56]. It is not considered an LGMD since it has been reported in only one family ^[5]. Its symptoms include skeletal muscle weakness and cardiac involvement ^[68].

LGMD2Z (LGMDR21) is caused by mutations in the POGLUT1 gene for protein O-glucosyltransferase 1, which is involved in protein transport ^[56]. The phenotype induces limb–girdle muscle weakness as well as a decrease in α-dystroglycan glycosylation and fatty replacement in muscles ^[69].

Three more myopathies are now considered as LGMDs:

Bethlem myopathy recessive (LGMDR22), caused by mutations in collagen 6 genes COL6A1, COL6A2, and COL6A3, which play roles in the extracellular matrix structure and muscle regeneration ^[5]. The phenotype is one of a progressive proximal weakness and ankle contracture. The subtle contracture of the interphalangeal joint is a specific sign of Bethlem myopathy ^[70].

Laminin α2-related muscular dystrophy (LGMDR23), associated with mutations in the LAMA2 gene, which is expressed as Laminin α2, a protein involved in myotube stability and apoptosis ^[71]. The phenotype is a progressive proximal muscle weakness and accounts for 36% of the patients reported having seizures without an epilepsy-related gene ^[72].

POMGNT2-related muscular dystrophy (LGMDR24) occurs due to mutations in the POMGnT2 gene, protein O-linked mannose β-1,4-N-Acetylglucosaminyl-transferase 2, which catalyzes reactions in α-dystroglycan ^[54]. The phenotype is one of a progressive proximal lower limb muscle weakness, along with possible ocular problems and cognitive impairment ^[73].

References

Walton, J.N.; Nattrass, F.J. On the classification, natural history and treatment of the myopathies. Brain 1954, 77, 169–231.
Reilich, P.; Krause, S.; Schramm, N.; Klutzny, U.; Bulst, S.; Zehetmayer, B.; Schneiderat, P.; Walter, M.C.; Schoser, B.; Lochmüller, H. A novel mutation in the myotilin gene (MYOT) causes a severe form of limb girdle muscular dystrophy 1A (LGMD1A). J. Neurol. 2011, 258, 1437–1444.
Selcen, D.; Engel, A.G. Mutations in myotilin cause myofibrillar myopathy. Neurology 2004, 62, 1363–1371.
Salmikangas, P.; van der Ven, P.F.; Lalowski, M.; Taivainen, A.; Zhao, F.; Suila, H.; Schröder, R.; Lappalainen, P.; Fürst, D.O.; Carpén, O. Myotilin, the limb-girdle muscular dystrophy 1A (LGMD1A) protein, cross-links actin filaments and controls sarcomere assembly. Hum. Mol. Genet. 2003, 12, 189–203.
Straub, V.; Murphy, A.; Udd, B.; Corrado, A.; Aymé, S.; Bönneman, C.; de Visser, M.; Hamosh, A.; Jacobs, L.; Khizanishvili, N.; et al. 229th ENMC international workshop: Limb girdle muscular dystrophies–Nomenclature and reformed classification Naarden, the Netherlands, 17–19 March 2017. Neuromuscul. Disord. 2018, 28, 702–710.
Rosenberg, R.N.; Pascual, J.M. Rosenberg’s Molecular and Genetic Basis of Neurological and Psychiatric Disease; Academic Press: London, UK, 2015.
Olivé, M.; Goldfarb, L.G.; Shatunov, A.; Fischer, D.; Ferrer, I. Myotilinopathy: Refining the clinical and myopathological phenotype. Brain 2005, 128, 2315–2326.
Muchir, A.; Bonne, G.; van der Kooi, A.J.; van Meegen, M.; Baas, F.; Bolhuis, P.A.; de Visser, M.; Schwartz, K. Identification of mutations in the gene encoding lamins A/C in autosomal dominant limb girdle muscular dystrophy with atrioventricular conduction disturbances (LGMD1B). Hum. Mol. Genet. 2000, 9, 1453–1459.
Muchir, A.; Van Engelen, B.G.; Lammens, M.; Mislow, J.M.; McNally, E.; Schwartz, K.; Bonne, G. Nuclear envelope alterations in fibroblasts from LGMD1B patients carrying nonsense Y259X heterozygous or homozygous mutation in lamin A/C gene. Exp. Cell Res. 2003, 291, 352–362.
Carbone, I.; Bruno, C.; Sotgia, F.; Bado, M.; Broda, P.; Masetti, E.; Panella, A.; Zara, F.; Bricarelli, F.D.; Cordone, G.; et al. Mutation in the CAV3 gene causes partial caveolin-3 deficiency and persistent elevated levels of serum creatine kinase. Neurology 2000, 54, 1373–1376.
Shah, D.S.; Nisr, R.B.; Stretton, C.; Krasteva-Christ, G.; Hundal, H.S. Caveolin-3 deficiency associated with the dystrophy P104L mutation impairs skeletal muscle mitochondrial form and function. J. Cachex-Sarcopenia Muscle 2020, 11, 838–858.
Lee, S.; Kim, S.Y.; Lim, B.C.; Kim, K.J.; Chae, J.H.; Cho, A. Expanding the Clinical and Genetic Spectrum of Caveolinopathy in Korea. Ann. Child Neurol. 2022, 30, 95–101.
Jonson, P.; Sarparanta, J.; Luque, H.; Udd, B. G.P.38 The LGMD1D gene DNAJB6: Its role in sarcomeric protein maintenance and aggregation. Neuromuscul. Disord. 2012, 22, 830–831.
Fan, L.I.; Meng, Y.U.; Jing, L.I.U.; Zhang, W.; He, L.Ü.; Yun, Y.U.A.N. Intrafamilial phenotypic variability of DNAJB6 mutation associated autosomal dominantly inherited myopathy: A family report and literature review. Chin. J. Contemp. Neurol. Neurosurg. 2021, 21, 204.
Nigro, V.; Savarese, M. Genetic basis of limb-girdle muscular dystrophies: The 2014 update. Acta Myol. 2014, 33, 1–12.
Hnia, K.; Ramspacher, C.; Vermot, J.; Laporte, J. Desmin in muscle and associated diseases: Beyond the structural function. Cell Tissue Res. 2015, 360, 591–608.
Carroll, L.S.; Walker, M.; Allen, D.; Marini-Bettolo, C.; Ditchfield, A.; Pinto, A.A.; Hammans, S.R. Desminopathy presenting as late onset bilateral facial weakness, with diagnosis supported by lower limb MRI. Neuromuscul. Disord. 2021, 31, 249–252.
Torella, A.; Fanin, M.; Mutarelli, M.; Peterle, E.; Blanco, F.D.V.; Rispoli, R.; Savarese, M.; Garofalo, A.; Piluso, G.; Morandi, L.; et al. Next-Generation Sequencing Identifies Transportin 3 as the Causative Gene for LGMD1F. PLoS ONE 2013, 8, e63536.
Angelini, C.; Peterle, E.; Fanin, M.; Cenacchi, G.; Nigro, V. P.5.10 Clinical and ultrastructural changes in transportinopathy. Neuromuscul. Disord. 2013, 23, 766–767.
Costa, R.; Rodia, M.T.; Pacilio, S.; Angelini, C.; Cenacchi, G. LGMD D2 TNPO3-Related: From Clinical Spectrum to Pathogenetic Mechanism. Front. Neurol. 2022, 13, 840683.
Vieira, N.M.; Naslavsky, M.S.; Licinio, L.; Kok, F.; Schlesinger, D.; Vainzof, M.; Sanchez, N.; Kitajima, J.P.; Gal, L.; Cavaçana, N.; et al. A defect in the RNA-processing protein HNRPDL causes limb-girdle muscular dystrophy 1G (LGMD1G). Hum. Mol. Genet. 2014, 23, 4103–4110.
Berardo, A.; Lornage, X.; Johari, M.; Evangelista, T.; Cejas, C.; Barroso, F.; Dubrovsky, A.; Bui, M.T.; Brochier, G.; Saccoliti, M.; et al. HNRNPDL-related muscular dystrophy: Expanding the clinical, morphological and MRI phenotypes. J. Neurol. 2019, 266, 2524–2534.
Li, R.Z.; Hou, J.; Wei, Y.; Luo, X.; Ye, Y.; Zhang, Y. hnRNPDL extensively regulates transcription and alternative splicing. Gene 2019, 687, 125–134.
Petruzzella, V.; Bisceglia, L.; Zoccolella, S.; Torraco, A.; Piemontese, M.R.; Amati, A.; Dell’Aglio, R.; de Bonis, P.; Artuso, L.; Santorelli, F.M.; et al. A new locus on 3p23-p25 for an autosomal dominant limb-girdle muscular dystrophy, LGMD1H. Eur. J. Hum. Genet. 2010, 18, 636–641.
Georganopoulou, D.G.; Moisiadis, V.G.; Malik, F.A.; Mohajer, A.; Dashevsky, T.M.; Wuu, S.T.; Hu, C.-K. A Journey with LGMD: From Protein Abnormalities to Patient Impact. Protein J. 2021, 40, 466–488.
Forsting, J.; Rohm, M.; Froeling, M.; Güttsches, A.-K.; Südkamp, N.; Roos, A.; Vorgerd, M.; Schlaffke, L.; Rehmann, R. Quantitative muscle MRI captures early muscle degeneration in calpainopathy. Sci. Rep. 2022, 12, 19676.
Salim, R.; Dahlqvist, J.R.; Khawajazada, T.; Kass, K.; Revsbech, K.L.; Borch, J.D.S.; Sheikh, A.M.; Vissing, J. Characteristic muscle signatures assessed by quantitative MRI in patients with Bethlem myopathy. J. Neurol. 2020, 267, 2432–2442.
Fu, J.; Zheng, Y.M.; Jin, S.Q.; Yi, J.F.; Liu, X.J.; Lyn, H.; Wang, Z.X.; Zhang, W.; Xiao, J.X.; Yuan, Y. “ target” and” Sandwich” signs in thigh muscles have high diagnostic values for collagen VI-related myopathies. Chin. Med. J. 2016, 129, 1811–1816.
Piluso, G.; Politano, L.; Aurino, S.; Fanin, M.; Ricci, E.; Ventriglia, V.M.; Belsito, A.; Totaro, A.; Saccone, V.; Topaloglu, H.; et al. Extensive scanning of the calpain-3 gene broadens the spectrum of LGMD2A phenotypes. J. Med. Genet. 2005, 42, 686–693.
Duguez, S.; Bartoli, M.; Richard, I. Calpain 3: A key regulator of the sarcomere? FEBS J. 2006, 273, 3427–3436.
Diers, A.; Carl, M.; Stoltenburg-Didinger, G.; Vorgerd, M.; Spuler, S. Painful enlargement of the calf muscles in limb girdle muscular dystrophy type 2B (LGMD2B) with a novel compound heterozygous mutation in DYSF. Neuromuscul. Disord. 2007, 17, 157–162.
Reyngoudt, H.; Smith, F.E.; Araújo, E.C.d.A.; Wilson, I.; Fernández-Torrón, R.; James, M.K.; Moore, U.R.; Díaz-Manera, J.; Marty, B.; Azzabou, N.; et al. Three-year quantitative magnetic resonance imaging and phosphorus magnetic resonance spectroscopy study in lower limb muscle in dysferlinopathy. J. Cachex-Sarcopenia Muscle 2022, 13, 1850–1863.
Pradhan, S. Clinical and magnetic resonance imaging features of ?diamond on quadriceps? sign in dysferlinopathy. Neurol. India 2009, 57, 172–175.
Mitsuhashi, S.; Kang, P.B. Update on the Genetics of Limb Girdle Muscular Dystrophy. Semin. Pediatr. Neurol. 2012, 19, 211–218.
Kefi, M.; Amouri, R.; Driss, A.; Ben Hamida, C.; Kunkel, L.; Hentati, F. Phenotype and sarcoglycan expression in Tunisian LGMD 2C patients sharing the same del521-T mutation. Neuromuscul. Disord. 2003, 13, 779–787.
Santos, M.O.; Coelho, P.; Roque, R.; Conceição, I. Very late-onset limb-girdle muscular dystrophy type 2D: A milder form with a normal muscle biopsy. J. Clin. Neurosci. 2020, 72, 471–473.
Laforêt, P.; Semplicini, C.; Dahlqvist, J.; Eymard, B.; Bello, L.; Witting, N.; Stojkovic, T.; Angelini, C.; Duno, M.; Leturcq, F.; et al. P.5.7 Limb-girdle muscular dystrophy type 2E: Clinical, genetic and histopathological features of 27 European patients. Neuromuscul. Disord. 2013, 23, 765–766.
Blain, A.M.; Straub, V.W. δ-Sarcoglycan-deficient muscular dystrophy: From discovery to therapeutic approaches. Skelet. Muscle 2011, 1, 13.
Mayans, O.; Van Der Ven, P.F.M.; Wilm, M.; Mues, A.; Young, P.; Fürst, D.O.; Wilmanns, M.; Gautel, M. Structural basis for activation of the titin kinase domain during myofibrillogenesis. Nature 1998, 395, 863–869.
Knöll, R.; Buyandelger, B. Z-disc transcriptional coupling, sarcomeroptosis and mechanopoptosis. Cell Biochem. Biophys. 2013, 66, 65–71.
Ikenberg, E.; Karin, I.; Ertl-Wagner, B.; Abicht, A.; Bulst, S.; Krause, S.; Schoser, B.; Reilich, P.; Walter, M.C. Rare diagnosis of telethoninopathy (LGMD2G) in a Turkish patient. Neuromuscul. Disord. 2017, 27, 856–860.
Choi, J.H.; Jeong, S.Y.; Kim, J.; Woo, J.S.; Lee, E.H. Tripartite motif-containing protein 32 regulates Ca2+ movement in skeletal muscle. Am. J. Physiol. Physiol. 2022, 323, C1860–C1871.
Schoser, B.G.; Frosk, P.; Engel, A.G.; Klutzny, U.; Lochmüller, H.; Wrogemann, K. Commonality of TRIM32 mutation in causing sarcotubular myopathy and LGMD2H. Ann. Neurol. 2005, 57, 591–595.
Rodriguez, H.; Rajasingham, T.; Ji, A.; Huang, E.; Sinha, U.; Sproule, D. P.171 Detection of alpha-dystroglycan glycation in muscle biopsies using a multiplexed western blot method. Neuromuscul. Disord. 2022, 32, S117.
Yamamoto, L.U.; Velloso, F.J.; Lima, B.L.; Fogaça, L.L.; de Paula, F.; Vieira, N.M.; Zatz, M.; Vainzof, M. Muscle Protein Alterations in LGMD2I Patients With Different Mutations in the Fukutin-related Protein Gene. J. Histochem. Cytochem. 2008, 56, 995–1001.
Monroy, J.A.; Powers, K.L.; Gilmore, L.A.; Uyeno, T.A.; Lindstedt, S.L.; Nishikawa, K.C. What Is the Role of Titin in Active Muscle? Exerc. Sport Sci. Rev. 2012, 40, 73–78.
Wang, G.; Lv, X.; Xu, L.; Zhang, R.; Yan, C.; Lin, P. Novel compound heterozygous mutations in the TTN gene: Elongation and truncation variants causing limb-girdle muscular dystrophy type 2J in a Han Chinese family. Neurol. Sci. 2022, 43, 3427–3433.
Manya, H.; Chiba, A.; Yoshida, A.; Wang, X.; Chiba, Y.; Jigami, Y.; Margolis, R.U.; Endo, T. Demonstration of mammalian protein O -mannosyltransferase activity: Coexpression of POMT1 and POMT2 required for enzymatic activity. Proc. Natl. Acad. Sci. USA 2003, 101, 500–505.
Geis, T.; Müller-Felber, W.; Schirmer, S.; Topaloglu, H.; Hehr, U. Broad Phenotypic Spectrum of A-Dystroglycanopathies due to POMT1 Mutations in 16 Families. Neuropediatrics 2014, 45, fp028.
Bolduc, V.; Marlow, G.; Boycott, K.M.; Saleki, K.; Inoue, H.; Kroon, J.; Itakura, M.; Robitaille, Y.; Parent, L.; Baas, F.; et al. Recessive mutations in the putative calcium-activated chloride channel Anoctamin 5 cause proximal LGMD2L and distal MMD3 muscular dystrophies. Am. J. Hum. Genet. 2010, 86, 213–221.
Godfrey, C.; Escolar, D.; Bsc, M.B.; Clement, E.M.; Mein, R.; Jimenez-Mallebrera, C.; Torelli, S.; Feng, L.; Brown, S.C.; Sewry, C.A.; et al. Fukutin gene mutations in steroid-responsive limb girdle muscular dystrophy. Ann. Neurol. 2006, 60, 603–610.
Puckett, R.L.; Moore, S.A.; Winder, T.L.; Willer, T.; Romansky, S.G.; Covault, K.K.; Campbell, K.P.; Abdenur, J.E. Further evidence of Fukutin mutations as a cause of childhood onset limb-girdle muscular dystrophy without mental retardation. Neuromuscul. Disord. 2009, 19, 352–356.
Østergaard, S.T.; Johnson, K.; Stojkovic, T.; Krag, T.; De Ridder, W.; De Jonghe, P.; Baets, J.; Claeys, K.G.; Fernández-Torrón, R.; Phillips, L.; et al. Limb girdle muscular dystrophy due to mutations in POMT2. J. Neurol. Neurosurg. Psychiatry 2018, 89, 506–512.
Halmo, S.M.; Singh, D.; Patel, S.; Wang, S.; Edlin, M.; Boons, G.J.; Moremen, K.W.; Live, D.; Wells, L. Protein O-Linked Mannose β-1,4-N-Acetylglucosaminyl-transferase 2 (POMGNT2) Is a Gatekeeper Enzyme for Functional Glycosylation of α-Dystroglycan. J. Biol. Chem. 2017, 292, 2101–2109.
Clement, E.; Godfrey, C.; Tan, J.; Brockington, M.; Torelli, S.; Feng, L.; Brown, S.C.; Jimenez-Mallebrera, C.; Sewry, C.A.; Longman, C.; et al. Mild POMGnT1 Mutations Underlie a Novel Limb-Girdle Muscular Dystrophy Variant. Arch. Neurol. 2008, 65, 137–141.
Taghizadeh, E.; Rezaee, M.; Barreto, G.E.; Sahebkar, A. Prevalence, pathological mechanisms, and genetic basis of limb-girdle muscular dystrophies: A review. J. Cell. Physiol. 2019, 234, 7874–7884.
Hara, Y.; Balci-Hayta, B.; Yoshida-Moriguchi, T.; Kanagawa, M.; de Bernabé, D.B.-V.; Gündeşli, H.; Willer, T.; Satz, J.S.; Crawford, R.W.; Burden, S.J.; et al. A Dystroglycan Mutation Associated with Limb-Girdle Muscular Dystrophy. N. Engl. J. Med. 2011, 364, 939–946.
Deev, R.V.; Bardakov, S.N.; Mavlikeev, M.O.; Yakovlev, I.A.; Umakhanova, Z.R.; Akhmedova, P.G.; Magomedova, R.M.; Chekmaryeva, I.A.; Dalgatov, G.D.; Isaev, A.A. Glu20Ter Variant in PLEC 1f Isoform Causes Limb-Girdle Muscle Dystrophy with Lung Injury. Front. Neurol. 2017, 8, 367.
Bögershausen, N.; Shahrzad, N.; Chong, J.X.; von Kleist-Retzow, J.-C.; Stanga, D.; Li, Y.; Bernier, F.P.; Loucks, C.M.; Wirth, R.; Puffenberger, E.G.; et al. Recessive TRAPPC11 Mutations Cause a Disease Spectrum of Limb Girdle Muscular Dystrophy and Myopathy with Movement Disorder and Intellectual Disability. Am. J. Hum. Genet. 2013, 93, 181–190.
Carss, K.J.; Stevens, E.; Foley, A.R.; Cirak, S.; Riemersma, M.; Torelli, S.; Hoischen, A.; Willer, T.; van Scherpenzeel, M.; Moore, S.A.; et al. Mutations in GDP-Mannose Pyrophosphorylase B Cause Congenital and Limb-Girdle Muscular Dystrophies Associated with Hypoglycosylation of α-Dystroglycan. Am. J. Hum. Genet. 2013, 93, 29–41.
Oestergaard, S.; Stojkovic, T.; Dahlqvist, J.; Bouchet-Seraphin, C.; Nectoux, J.; Leturcq, F.; Cossée, M.; Solé, G.; Thomsen, C.; Krag, T.; et al. Muscle involvement in limb-girdle muscular dystrophy with GMPPB deficiency (LGMD2T). Neurol. Genet. 2016, 2, e112.
Roscioli, T.; Kamsteeg, E.-J.; Buysse, K.; Maystadt, I.; van Reeuwijk, J.; Elzen, C.v.D.; van Beusekom, E.; Riemersma, M.; Pfundt, R.; Vissers, L.E.L.M.; et al. Mutations in ISPD cause Walker-Warburg syndrome and defective glycosylation of α-dystroglycan. Nat. Genet. 2012, 44, 581–585.
Magri, F.; Colombo, I.; Del Bo, R.; Previtali, S.C.; Brusa, R.; Ciscato, P.; Scarlato, M.; Ronchi, D.; D’angelo, M.G.; Corti, S.; et al. ISPD mutations account for a small proportion of Italian Limb Girdle Muscular Dystrophy cases. BMC Neurol. 2015, 15, 172.
Muraoka, T.; Murao, K.; Imachi, H.; Kikuchi, F.; Yoshimoto, T.; Iwama, H.; Hosokawa, H.; Nishino, I.; Fukuda, T.; Sugie, H.; et al. Novel Mutations in the Gene Encoding Acid α-1,4-glucosidase in a Patient with Late-onset Glycogen Storage Disease Type II (Pompe Disease) with Impaired Intelligence. Intern. Med. 2011, 50, 2987–2991.
Savarese, M.; Torella, A.; Musumeci, O.; Angelini, C.; Astrea, G.; Bello, L.; Bruno, C.; Comi, G.P.; Di Fruscio, G.; Piluso, G.; et al. Targeted gene panel screening is an effective tool to identify undiagnosed late onset Pompe disease. Neuromuscul. Disord. 2018, 28, 586–591.
Chardon, J.W.; Smith, A.; Woulfe, J.; Pena, E.; Rakhra, K.; Dennie, C.; Beaulieu, C.; Huang, L.; Schwartzentruber, J.; Hawkins, C.; et al. LIMS2 mutations are associated with a novel muscular dystrophy, severe cardiomyopathy and triangular tongues. Clin. Genet. 2015, 88, 558–564.
Gangfuß, A.; Hentschel, A.; Heil, L.; Gonzalez, M.; Schönecker, A.; Depienne, C.; Nishimura, A.; Zengeler, D.; Kohlschmidt, N.; Sickmann, A.; et al. Proteomic and morphological insights and clinical presentation of two young patients with novel mutations of BVES (POPDC1). Mol. Genet. Metab. 2022, 136, 226–237.
Ghaoui, R.; Benavides, T.; Lek, M.; Waddell, L.B.; Kaur, S.; North, K.N.; MacArthur, D.G.; Clarke, N.F.; Cooper, S.T. TOR1AIP1 as a cause of cardiac failure and recessive limb-girdle muscular dystrophy. Neuromuscul. Disord. 2016, 26, 500–503.
Servián-Morilla, E.; Cabrera-Serrano, M.; Johnson, K.; Pandey, A.; Ito, A.; Rivas, E.; Chamova, T.; Muelas, N.; Mongini, T.; Nafissi, S.; et al. POGLUT1 biallelic mutations cause myopathy with reduced satellite cells, α-dystroglycan hypoglycosylation and a distinctive radiological pattern. Acta Neuropathol. 2020, 139, 565–582.
Park, H.J.; Choi, Y.C.; Kim, S.M.; Kim, S.H.; Hong, Y.B.; Yoon, B.R.; Chung, K.W.; Choi, B.O. Molecular genetic diagnosis of a Bethlem myopathy family with an autosomal-dominant COL6A1 mutation, as evidenced by exome sequencing. J. Clin. Neurol. 2015, 11, 183–187.
Vachon, P.H.; Loechel, F.; Xu, H.; Wewer, U.M.; Engvall, E. Merosin and laminin in myogenesis; specific requirement for merosin in myotube stability and survival. J. Cell Biol. 1996, 134, 1483–1497.
Huang, X.; Tan, D.; Zhang, Z.; Ge, L.; Liu, J.; Ding, J.; Yang, H.; Wei, C.; Chang, X.; Yuan, Y.; et al. Unique genotype-phenotype correlations within LAMA2-related limb girdle muscular dystrophy in Chinese patients. Front. Neurol. 2023, 14, 1158094.
Endo, Y.; Dong, M.; Noguchi, S.; Ogawa, M.; Hayashi, Y.K.; Kuru, S.; Sugiyama, K.; Nagai, S.; Ozasa, S.; Nonaka, I.; et al. Milder forms of muscular dystrophy associated with POMGNT2 mutations. Neurol. Genet. 2015, 1, e33.

© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.

Upload a video for this entry

Information

Subjects: Neurosciences

Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :

Camille Bouchard

Jacques P. Tremblay

View Times: 345

Update Date: 27 Jul 2023

Table of Contents

Video Upload Options

Confirm