Protein and genetic diagnosis of limb girdle muscular dystrophy type 2A: The yield and the pitfalls

Muscle and Nerve

Volumn 52, Issue 2, 2015, Pages 163-173

  Fanin, Marina ^a   Angelini, Corrado ^b  

^a Centro Biomedico Pietro d'Abano via Orus 2   (Italy)

^b IRCCS SAN CAMILLO HOSPITAL   (Italy)

Author keywords

Calpain 3; Calpainopathy; Genetic diagnosis; Immunoblot analysis; LGMD2A; Limb girdle muscular dystrophy; Mutation detection; Protein testing

Indexed keywords

CALPAIN 3; COMPLEMENTARY DNA; GENOMIC DNA; CALPAIN; CAPN3 PROTEIN, HUMAN; MUSCLE PROTEIN;

ASTHENIA; CLINICAL FEATURE; DIAGNOSTIC ERROR; DIFFERENTIAL DIAGNOSIS; DNA SEQUENCE; GENE IDENTIFICATION; GENE MUTATION; GENETIC EPIDEMIOLOGY; GENETIC SCREENING; GENOTYPE PHENOTYPE CORRELATION; HETEROZYGOTE; HISTOPATHOLOGY; HUMAN; HYPEREOSINOPHILIA; IMMUNOBLOTTING; IMMUNOHISTOCHEMISTRY; JOINT CONTRACTURE; LIMB GIRDLE MUSCULAR DYSTROPHY; LIMB GIRDLE MUSCULAR DYSTROPHY TYPE 2A; MOLECULAR DIAGNOSIS; MOLECULAR PATHOLOGY; MUSCLE ATROPHY; MUSCLE BIOPSY; MUSCLE TISSUE; MUSCLE WEAKNESS; MUTATIONAL ANALYSIS; MYALGIA; MYOPATHY; MYOSITIS; PHENOTYPE; PRENATAL DIAGNOSIS; PREVALENCE; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN DEFICIENCY; PROTEIN FUNCTION; REVIEW; ANIMAL; DEFICIENCY; GENETICS; METABOLISM; MUSCULAR DYSTROPHIES, LIMB-GIRDLE; MUTATION; PROCEDURES;

ANIMALS; CALPAIN; GENETIC TESTING; HUMANS; MUSCLE PROTEINS; MUSCULAR DYSTROPHIES, LIMB-GIRDLE; MUTATION;

EID: 84937435413     PISSN: 0148639X     EISSN: 10974598     Source Type: Journal    
DOI: 10.1002/mus.24682     Document Type: Review

References (118)

1. Fardeau M, Hillaire D, Mignard C, Feingold N, Feingold J, Mignard D, et al. Juvenile limb girdle muscular dystrophy. Clinical, histopathological and genetic data from a small community living in the Reunion Island. Brain 1996;119:295-308.
2. van der Kooi AJ, Barth PG, Busch HF, de Haan R, Ginjaar HB, van Essen AJ, et al. The clinical spectrum of limb girdle muscular dystrophy. A survey in The Netherlands. Brain 1996;119:1471-1480.
3. Krahn M, Lopez de Munain A, Streichenberger N, Bernard R, Pécheux C, Testard H, et al. CAPN3 mutations in patients with idiopathic eosinophilic myositis. Ann Neurol 2006;59:905-911.
4. Krahn M, Goicoechea M, Hanisch F, Groen E, Bartoli M, Pécheux C, et al. Eosinophilic infiltration related to CAPN3 mutations: a pathophysiological component of primary calpainopathy? Clin Genet 2011;80:398-402.
5. Brown RH, Amato A. Calpainopathy and eosinophilic myositis. Ann Neurol 2006;59:875-877.
6. Penisson-Besnier I, Richard I, Dubas F, Beckmann JS, Fardeau M. Pseudo-metabolic expression and phenotypic variability of calpain deficiency in two siblings. Muscle Nerve 1998;21:1078-1080.
7. Pollitt C, Anderson LV, Pogue R, Davison K, Pyle A, Bushby KM. The phenotype of calpainopathy: diagnosis based on a multidisciplinary approach. Neuromuscul Disord 2001;11:287-296.
8. Mercuri E, Bushby K, Ricci E, Knight R, Pane M, Kinali M, et al. Muscle MRI findings in patients with limb girdle muscular dystrophy with calpain 3 deficiency (LGMD2A) and early contractures. Neuromuscul Disord 2005;15:164-171.
9. Borsato C, Padoan R, Stramare R, Fanin M, Angelini C. Limb girdle muscular dystrophies type 2A and 2B: clinical and radiologic aspects. Basic Appl Myol 2006;16:17-25.
10. Stramare R, Beltrame V, Dal Borgo R, Gallimberti AL, Frigo AC, Pegoraro AC, et al. MRI in the assessment of muscular pathology: a comparison between limb-girdle muscular dystrophies, hyaline body myopathies and myotonic dystrophies. Radiol Med 2010;115:585-599.
11. Ten Dam L, van der Kooi A, van Wattingen M, de Haan RJ, de Visser M. Reliability and accuracy of skeletal muscle imaging in limb-girdle muscular dystrophies. Neurology 2012;79:1716-1723.
12. Fanin M, Nascimbeni AC, Angelini C. Muscle atrophy in limb girdle muscular dystrophy 2A: a morphometric and molecular study. Neuropathol Appl Neurobiol 2013;39:762-771.
13. Fanin M, Nascimbeni AC, Angelini C. Gender difference in limb-girdle muscular dystrophy: a muscle fiber morphometric study in 101 patients. Clin Neuropathol 2014;33:179-185.
14. Angelini C, Nardetto L, Borsato C, Padoan R, Fanin M, Nascimbeni AC, et al. The clinical course of calpainopathy (LGMD2A) and dysferlinopathy (LGMD2B). Neurol Res 2010;32:41-46.
15. Urtasun M, Saenz A, Roudaut C, Poza JJ, Urtizberea JA, Cobo AM, et al. Limb girdle muscular dystrophy in Guipuzcoa (Basque Country, Spain). Brain 1998;121:1735-1747.
16. Sveen ML, Thuna JJ, Kober L, Vissing J. Cardiac involvement in patients with limb-girdle muscular dystrophy type 2 and Becker muscular dystrophy. Arch Neurol 2008;65:1196-1201.
17. Dirik E, Aydin A, Kurul S, Sahin B. Limb girdle muscular dystrophy type 2A presenting with cardiac arrest. Pediatr Neurol 2001;24:235-237.
18. Okere A, Reddy SS, Gupta S, Shinnar M. A cardiomyopathy in a patient with limb girdle muscular dystrophy type 2A. Circ Heart Fail 2013;6:e12-e13.
19. Hashiguchi S, Adachi K, Arii Y, Kashiwagi S, Sato M, Kagawa N, et al. A clinic-pathological investigation of two autopsy cases of calpainopathy (LGMD2A) [in Japanese]. Brain Nerve 2014;66:1097-1102.
20. Leidenroth A, Sorte HS, Gilfillan G, Ehrlich M, Lyle R, Hewitt JE. Diagnosis by sequencing: correction of misdiagnosis from FSHD2 to LGMD2A by whole-exome analysis. Eur J Hum Genet 2012;20:999-1003.
21. Sacconi S, Camano P, de Greef JC, Lemmers RJ, Salviati L, Boileau P, et al. Patients with a phenotype consistent with facio scapulo humeral muscular dystrophy display genetic and epigenetic heterogeneity. J Med Genet 2012;49:41-46.
22. Arikawa E, Hoffman EP, Kaido M, Nonaka I, Sugita H, Arahata K. The frequency of patients with dystrophin abnormalities in a limb-girdle patient population. Neurology 1991;41:1491-1496.
23. Georgieva B, Todorova A, Kremensky I, Tournev I, Mitev V, Plageras P. 550delA mutation in the calpain 3 (CAPN3) gene: DMD/BMD, SMA, or LGMD2A clinically misdiagnosed cases. Am J Med Genet 2005;136A:399-400.
24. Chae J, Minami N, Jin Y, Nakagawa M, Murayama K, Igarashi F, et al. Calpain 3 gene mutations: genetic and clinico-pathologic findings in limb-girdle muscular dystrophy. Neuromuscul Disord 2001;11:547-555.
25. Vainzof M, de Paula F, Tsanaclis AM, Zatz M. The effect of calpain 3 deficiency on the pattern of muscle degeneration in the earliest stages of LGMD2A. J Clin Pathol 2003;56:624-626.
26. Rosales XQ, Malik V, Sneh A, Chen L, Lewis S, Kota J, et al. Impaired regeneration in LGMD2A supported by increased Pax7-positive satellite cell content and muscle-specific microRNA dysregulation. Muscle Nerve 2013;47:731-739.
27. Hermanová M, Zapletálova E, Sedlácková J, Chrobácková T, Letocha O, Kroupová I, et al. Analysis of histopathological and molecular pathologic findings in Czech LGMD2A patients. Muscle Nerve 2006;33:424-432.
28. Pathak P, Sharma MC, Sarkar C, Jha P, Suri V, Mohd H, et al. Limb girdle muscular dystrophy type 2A in India: a study based on semi-quantitative protein analysis, with clinical and histopathological correlations. Neurol India 2010;58:549-554.
29. Luo SS, Xi JY, Lu JH, Zhao CB, Zhu WH, Lin J, et al. Clinical and pathological features in 15 Chinese patients with calpainopathy. Muscle Nerve 2011;43:402-409.
30. Fanin M, Nardetto L, Nascimbeni AC, Tasca E, Spinazzi M, Padoan R, et al. Correlations between clinical severity, genotype and muscle pathology in LGMD2A. J Med Genet 2007;44:609-614.
31. Kawai H, Akaike M, Kunishige M, Inui T, Adachi K, Kimura C, et al. Clinical, pathological, and genetic features of limb-girdle muscular dystrophy type 2A with new calpain 3 gene mutations in seven patients from three Japanese families. Muscle Nerve 1998;21:1493-1501.
32. Hauerslev S, Sveen ML, Duno M, Angelini C, Vissing J, Krag TO. Calpain 3 is important for muscle regeneration: evidence from patients with limb girdle muscular dystrophies. BMC Musculoskel Disord 2012;13:43-53.
33. Piluso G, Politano L, Aurino S, Fanin M, Ricci E, Ventriglia VM, et al. Extensive scanning of the calpain-3 gene broadens the spectrum of LGMD2A phenotypes. J Med Genet 2005;42:686-693.
34. de Paula F, Vainzof M, Passos-Bueno MR, de Cassia M, Pavanaello R, Matioli SR, et al. Clinical variability in calpainopathy: what makes the difference? Eur J Hum Genet 2002;10:825-832.
35. Zatz M, De Paula F, Starling A, Vainzof M. The 10 autosomal recessive limb-girdle muscular dystrophies. Neuromuscul Disord 2003;13:532-544.
36. Beckmann JS, Richard I, Hillaire D, Broux O, Antignac C, Bois E, et al. A gene for limb-girdle muscular dystrophy maps to chromosome 15 by linkage. C R Acad Sci III 1991;312:141-148.
37. Young K, Foroud T, Williams P, Jackson CE, Beckmann JS, Cohen D, et al. Confirmation of linkage of limb-girdle muscular dystrophy type 2 to chromosome 15. Genomics 1992;13:1370-1371.
38. Passos-Bueno MR, Richard I, Vainzof M, Fougerousse F, Weissenbach J, Broux O, et al. Evidence of genetic heterogeneity in the autosomal recessive adult forms of limb-girdle muscular dystrophy following linkage analysis with 15q probes in Brazilian families. J Med Genet 1993;30:385-387.
39. Fougerousse F, Broux O, Richard I, Allamand V, de Souza P, Bourg N, et al. Mapping of a chromosome 15 region involved in limb girdle muscular dystrophy. Hum Mol Genet 1994;3:285-293.
40. Allamand V, Broux O, Richard I, Fougerousse F, Chiannilkulchai N, Bourg N, et al. Preferential localization of the limb-girdle muscular dystrophy type 2A gene in the proximal part of a 1-cM 15q15.1-q15.3 interval. Am J Hum Genet 1995;56:1417-1430.
41. Chiannilkulchai N, Pasturaud P, Richard I, Auffray C, Beckmann JS. A primary expression map of the chromosome 15q15 region containing the recessive form of limb-girdle muscular dystrophy (LGMD2A) gene. Hum Mol Genet 1995;4:717-725.
42. Richard I, Broux O, Allamand V, Fougerousse F, Chiannilkulchai N, Bourg N, et al. Mutations in the proteolytic enzyme calpain-3 cause limb girdle muscular dystrophy type 2A. Cell 1995;81:27-40.
43. Anderson LV, Davison K, Moss JA, Richard I, Fardeau M, Tomé FM, et al. Characterization of monoclonal antibodies to calpain-3 and protein expression in muscle from patients with limb girdle muscular dystrophy type 2A. Am J Pathol 1998;153:1169-1179.
44. Anderson LV, Davison K. Multiplex Western blotting system for the analysis of muscular dystrophy proteins. Am J Pathol 1999;154:1017-1022.
45. Ibi T, Jing L, Nakao N, Minami N, Sahashi K. A case of LGMD2A identified with both western blot analysis and immunostaining of calpain-3 in biopsied muscle. Rinsho Shinkeigaku 2000;40:1023-1027.
46. Kolski HK, Hawkins C, Zatz M, de Paula F, Biggar D, Alman B, et al. Diagnosis of limb girdle muscular dystrophy 2A by immunohistochemical techniques. Neuropathology 2008;28:264-268.
47. Charlton R, Henderson M, Richards J, Hudson J, Straub V, Bushby K. Immunohistochemical analysis of calpain-3: advantages and limitations. Neuromuscul Disord 2009;19:449-457.
48. Fanin M, Fulizio L, Nascimbeni AC, Spinazzi M, Piluso G, Politano L, et al. Molecular diagnosis of LGMD2A: gene mutation analysis or protein testing? Hum Mutat 2004;24:52-62.
49. Anderson LV, Harrison RM, Pogue R, Vafiadaki E, Pollitt C, Davison K, et al. Secondary reduction in calpain-3 expression in patients with limb girdle muscular dystrophy type 2B and Miyoshi myopathy (primary dysferlinopathies). Neuromuscul Disord 2000;10:553-559.
50. Haravuori H, Vihol A, Straub V, Auranen M, Richard I, Marchand S, et al. Secondary calpain-3 deficiency in 2q-linked muscular dystrophy: titin is the candidate gene. Neurology 2001;56:869-877.
51. Fanin M, Nascimbeni A, Fulizio L, Trevisan CP, Meznaric-Petrusa M, Angelini C. Loss of calpain-3 autocatalytic activity in LGMD2A patients with normal protein expression. Am J Pathol 2003;163:1929-1936.
52. Talim B, Ognibene A, Mattioli E, Richard I, Anderson LV, Merlini L. Normal calpain expression in genetically confirmed limb girdle muscular dystrophy type 2A. Neurology 2001;56:692-693.
53. Milic A, Daniele N, Löchmuller H, Mora M, Comi GP, Moggio M, et al. A third of LGMD2A biopsies have normal calpain 3 proteolytic activity as determined by an in vitro assay. Neuromuscul Disord 2007;17:148-156.
54. Groen EJ, Charlton R, Barresi R, Anderson LV, Eagle M, Hudson J, et al. Analysis of the UK diagnostic strategy for limb girdle muscular dystrophy 2A. Brain 2007;130:3237-3249.
55. Fanin M, Nascimbeni AC, Angelini C. Screening of calpain-3 autolytic activity in LGMD muscle: a functional map of CAPN3 gene mutations. J Med Genet 2007;44:38-43.
56. Fanin M, Nascimbeni AC, Tasca E, Angelini C. How to tackle the diagnosis of limb-girdle muscular dystrophy 2A. Eur J Hum Genet 2009;17:598-603.
57. Fanin M, Pegoraro E, Matsuda-Asada C, Brown RH, Angelini C. Calpain-3 and dysferlin protein screening in limb-girdle muscular dystrophy and myopathy patients. Neurology 2001;56:660-665.
58. Cooper ST, Lo HP, North KN. Single section Western blot: improving the molecular diagnosis of the muscular dystrophies. Neurology 2003;61:93-97.
59. Lanzillo R, Aurino S, Fanin M, Aguennoz M, Vitale F, Fiorillo C, et al. Early onset calpainopathy with normal non-functional calpain-3 level. Dev Med Child Neurol 2006;48:304-306.
60. Garnham CP, Hanna RA, Chou JS, Low KE, Gourlay K, Campbell RL, et al. Limb girdle muscular dystrophy type 2A can result from accelerated autoproteolytic inactivation of calpain 3. Biochemistry 2009;48:3457-3467.
61. Luo SS, Xi JY, Zhu WH, Zhao CB, Lu JH, Lin J, et al. Genetic variability and clinical spectrum of Chinese patients with limb girdle muscular dystrophy type 2A. Muscle Nerve 2012;46:723-729.
62. Fanin M, Nardetto L, Nascimbeni AC, Tasca E, Spinazzi M, Padoan R, et al. Correlations between clinical severity, genotype and muscle pathology in LGMD2A. J Med Genet 2007;44:609-614.
63. Perez F, Vital A, Martin-Negrier ML, Ferrer X, Sole G. Diagnostic procedure of limb girdle muscular dystrophies 2A or calpainopathy: French cohort from a neuromuscular center (Bordeaux). Rev Neurol 2010;166:502-508.
64. Kramerova I, Beckmann JS, Spencer MJ. Molecular and cellular basis of calpainopathy (limb girdle muscular dystrophy type 2A. Biochem Biophys Acta 2007;1772:128-144.
65. Richard I, Roudaut C, Saenz A, Pogue R, Grimbergen JE, Anderson LV, et al. Calpainopathy-a survey of mutations and polymorphisms. Am J Hum Genet 1999;64:1524-1540.
66. Blázquez L, Azpitarte M, Sáenz A, Goicoechea M, Otaegui D, Ferrer X, et al. Characterization of novel CAPN3 isoforms in white blood cells: an alternative approach for limb girdle muscular dystrophy 2A diagnosis. Neurogenetics 2008;9:173-182.
67. Nascimbeni AC, Fanin M, Tasca E, Angelini C. Transcriptional and translational effects of intronic CAPN3 gene mutations. Hum Mutat 2010;31:1658-1669.
68. Krahn M, Pécheux C, Chapon F, Beroud C, Drouin-Garraud V, Laforet P, et al. Transcriptional explorations of CAPN3 identify novel splicing mutations, a large-sized genomic deletion and evidence for messenger RNA decay. Clin Genet 2007;72:582-592.
69. Richard I, Beckmann JS. How neutral are synonymous codon mutations? Nat Genet 1995;10:259.
70. Duno M, Sveen ML, Schwartz M, Vissing J. cDNA analysis of CAPN3 enhance mutations detection and reveal a low prevalence of LGMD2A patients in Denmark. Eur J Hum Genet 2008;16:935-940.
71. Salem IH, Hsairi I, Mezghani N, Kenoun H, Triki C, Fakhfakh F. CAPN3 mRNA processing alterations caused by splicing mutation associated with novel genomic rearrangement of Alu elements. J Hum Genet 2012;57:92-100.
72. Spurdle AB, Couch FJ, Hogerjorst FBL, Radice P, Sinilnikova OH. Prediction and assessment of splicing, alterations: implications for clinical testing. Hum Mut 2008;29:304-337.
73. Haffner K, Speer A, Hubner C, Voit T, Oexle K. A small in-frame deletion within the protease domain of muscle-specific calpain, p94, causes early-onset limb-girdle muscular dystrophy 2A. Hum Mutat 1998;S1(suppl 1):298-300.
74. Stehliková K, Zapletalová E, Sedlácková J, Hermanová M, Vondrácek P, Marícová T, et al. Quantitative analysis of CAPN3 transcripts in LGMD2A patients: involvement of nonsense-mediated mRNA decay. Neuromuscul Disord 2007;17:143-147.
75. Papic L, Fischer D, Trajanoski S, Hoftberger R, Fischer C, Ströbel T, et al. SNP-array based whole genome homozygosity mapping: a quick and powerful tool to achieve an accurate diagnosis in LGMD2 patients. Eur J Med Genet 2011;54:214-219.
76. Bartoli M, Nègre P, Wein N, Bourgeois P, Péchaux C, Lévy N, et al. Validation of comparative genomic hybridization arrays for the detection of genomic rearrangements of the calpain-3 and dysferlin genes. Clin Genet 2012;81:99-101.
77. Bushby K. Diagnosis and management of the limb girdle muscular dystrophies. Pract Neurol 2009;9:314-323.
78. Piluso G, Dionisi M, Del Vecchio Blanco F, Torella A, Aurino S, Savarese M, et al. Motor chip: a comparative genomic hybridization microarray for copy-number mutations in 245 neuromuscular disorders. Clin Chem 2001;57:1584-1596.
79. Bartoli M, Desvignes JP, Levy N, Krahn M. Exome sequencing as a second-tier diagnostic approach for clinically suspected dysferlinopathy patients. Muscle Nerve 2014;50:1007-1010.
80. Nigro V, Piluso G. Next generation sequencing (NGS) strategies for the genetic testing of myopathies. Acta Myol 2012;31:196-200.
81. Nigro V, Savarese M. Genetic basis of limb-girdle muscular dystrophies: the 2014 update. Acta Myol 2014;33:1-12.
82. Leiden Muscular Dystrophy Pages. Available at: http://www.dmd.nl/.
83. Ermolova N, Kramerova I, Spencer MJ. Autolytic activation of calpain-3 proteinase is facilitated by calmodulin protein. J Biol Chem 2015;290:996-1004.
84. Dinçer P, Leturcq F, Richard I, Piccolo F, Yalnizoglu D, de Toma C, et al. A biochemical, genetic, and clinical survey of autosomal recessive limb girdle muscular dystrophies in Turkey. Ann Neurol 1997;42:222-229.
85. Pogoda TV, Krakhmaleva IN, Lipatova NA, Shakhovskaya NI, Shishkin SS, Limborska SA. High incidence of 550delA mutation of CAPN3 in LGMD2A from Russia. Hum Mutat 2000;15:295.
86. Canki-Klain N, Milic A, Kovac B, Trlaja A, Grgicevic D, Zurak N, et al. Prevalence of the 550delA mutation in calpainopathy (LGMD2A) in Croatia. Am J Med Genet A 2004;125:152-156.
87. Chrobáková T, Hermanová M, Kroupová I, Vondrácek P, Maríková T, Mazanec R, et al. Mutations in Czech LGMD2A patients revealed by analysis of calpain3 mRNA and their phenotypic outcome. Neuromuscul Disord 2004;14:659-665.
88. Fanin M, Nascimbeni AC, Fulizio L, Angelini C. The frequency of limb girdle muscular dystrophy 2A in northeastern Italy. Neuromuscul Disord 2005;15:218-224.
89. Milic A, Canki-Klain N. Calpainopathy (LGMD2A) in Croatia: molecular and haplotype analysis. Croat Med J 2005;46:657-663.
90. Balci B, Aurino S, Haliloglu G, Talim B, Erdim S, Akcören Z, et al. Calpain-3 mutations in Turkey. Eur J Pediatr 2006;165:293-298.
91. Todorova A, Georgieva B, Tournev I, Todorov T, Bogdanova N, Mitev V. A large deletion and novel point mutations in the calpain-3 gene (CAPN3) in Bulgarian LGMD2A patients. Neurogenetics 2007;8:225-229.
92. Hanisch F, Müller CR, Grimm D, Xue L, Traufeller K, Merkenshlager A, et al. Frequency of calpain-3 c.550delA mutation in limb girdle muscular dystrophy type 2 and isolated hyperCKemia in German patients. Clin Neuropathol 2007;26:157-163.
93. Dadali EL, Shagina OA, Ryzhkova OP, Rudenskaia GE, Fedotov VP, Poliakov AV. Clinical-genetic characteristics of limb girdle-muscular dystrophy. Zh Nevrol Psikhiatr Im SS Korsakova 2010;110:79-83.
94. Nadaj-Pakleza AA, Dorobek M, Nestorowicz K, Ryniewicz B, Szmidt-Salkowska E, Kaminska AM. Muscle pathology in 31 patients with calpain-3 gene mutations. Neurol Neurochir Pol 2013;47:214-222.
95. Stehlíková K, Skíloví D, Zídková J, Mrázová L, Vondráček P, Mazanek R, et al. Autosomal recessive limb girdle muscular dystrophies in the Czech Republic. BMC Neurol 2014;14:154-162.
96. Hermanová M, Zapletalová E, Sedlácková J, Chrobácková T, Lertocha O, Kroupová I, et al. Analysis of histopathologic and molecular pathologic findings in Czech LGMD2A patients. Muscle Nerve 2006;33:424-432.
97. Cobo AM, Sáenz A, Poza JJ, Urtasun M, Indakoetxea B, Urtizberea AT, et al. A common haplotype associated with the Basque 2362AG>TCATCT mutation in the muscular calpain-3 gene. Hum Biol 2004;76:731-741.
98. Minami N, Nishino I, Kobayashi O, Ikezoe K, Goto Y, Nonaka I. Mutations of calpain 3 gene in patients with sporadic limb-girdle muscular dystrophy in Japan. J Neurol Sci 1999;171:31-37.
99. Fanin M, Benedicenti F, Fritegotto C, Nascimbeni AC, Peterle E, Stanzial F, et al. An intronic mutation causes severe LGMD2A in a large inbred family belonging to a genetic isolate in the Alps. Clin Genet 2012;82:601-602.
100. Ankala A, Kohn JN, Dastur R, Gaitonde P, Khadilkar SV, Hegde MR. Ancestral founder mutations in calpain-3 in the Indian Agarwal community: historical, clinical, and molecular perspective. Muscle Nerve 2013;47:931-987.
101. Blázquez L, Aiastui A, Goicoechea M, Martins de Araujao DM, Avil A, Beley C, et al. In vitro correction of a pseudoexon-generating deep intronic mutation in LGMD2A by antisense oligonucleotides and modified small nuclear RNAs. Hum Mutat 2013;34:1387-1395.
102. Jaka O, Azpitarte M, Paisán-Ruiz C, Zulaika M, Casas-Fraile L, Sanz R, et al. Entire CAPN3 gene deletion in a patient with limb girdle muscular dystrophy type 2A. Muscle Nerve 2014;50:448-453.
103. Sáenz A, Leturcq F, Cobo AM, Poza JJ, Ferrer X, Otaegui D, et al. LGMD2A: genotype-phenotype correlations based on a large mutational survey on calpain-3 gene. Brain 2005;128:732-742.
104. Bushby KM, Beckmann JS. The 105th ENMC sponsored workshop: pathogenesis in the non-sarcoglycan limb-girdle muscular dystrophies. Neuromuscul Disord 2003;13:80-90.
105. Lo HP, Cooper ST, Evesson FJ, Seto JT, Choitis AM, Tay V, et al. Limb girdle muscular dystrophy: diagnostic evaluation, frequency and clues to pathogenesis. Neuromuscul Disord 2008;18:34-44.
106. Shin JH, Kim HS, Lee CH, Kim CM, Park KH, Kim DS. Mutations of CAPN3 in Korean patients with limb girdle muscular dystrophy. J Korean Med Sci 2007;22:463-469.
107. Chou FL, Angelini C, Daentl D, Garcia C, Greco C, Hausmanowa-Petrusawicz I, et al. Calpain III mutation analysis of a heterogeneous limb-girdle muscular dystrophy population. Neurology 1999;52:1015-1020.
108. Moore SA, Shilling CJ, Westra S, Wall C, Wicklund MP, Stolle C, et al. Limb-girdle muscular dystrophy in the United States. J Neuropathol Exp Neurol 2006;65:995-1003.
109. Gómez-Díaz B, Rosas-Vargas H, Roque-Ramirez B, Meza-Espinoza P, Ruano-Calderón LA, Fernández-Valverde F, et al. Immunodetection analysis of muscular dystrophies in Mexico. Muscle Nerve 2012;45:338-345.
110. Mahmood OA, Jiang X, Zhang Q. Limb-girdle muscular dystrophy subtypes: first-reported cohort from northeastern China. Neural Regen Res 2013;8:1907-1918.
111. van der Kooi AJ, Frankhuizen WS, Barth PG, Howeler CJ, Padberg GW, Spaans F, et al. Limb girdle muscular dystrophy in the Netherlands: gene defect identified in half the families. Neurology 2007;68:2125-2128.
112. Norwood FL, Harling C, Chinnery PF, Eagle M, Bushby K, Straub V. Prevalence of genetic muscle disease in Northern England: in depth analysis of a muscle clinic population. Brain 2009;132:3175-3186.
113. Guglieri M, Magri F, D'Angelo MG, Prelle A, Morandi L, Rodolico C, et al. Clinical, molecular, and protein correlations in a large sample of genetically diagnosed Italian limb girdle muscular dystrophy patients. Hum Mutat 2008;29:258-266.
114. Fanin M, Nascimbeni AC, Aurino S, Tasca E, Pegararo E, Nigro V, et al. Frequency of LGMD gene mutations in Italian patients with distinct clinical phenotypes. Neurology 2009;72:1432-1435.
115. Zatz M, Vainzof M, Passos-Bueno MR. Limb girdle muscular dystrophy: one gene with different phenotypes, one phenotype with different genes. Curr Opin Neurol 2000;13:511-517.
116. Richard I, Brenguier L, Dinçer P, Roudat C, Bady B, Burgunder JM, et al. Multiple independent molecular etiology for limb girdle muscular dystrophy type 2A patients from various geographical origins. Am J Hum Genet 1997;60:1128-1138.
117. Meznaric-Petrusa MMP, Zidar J, Zupancic N, et al. Clinical, molecular and genetic features of calpainopathy in Slovenia. Neuromuscul Disord 2002;12(7-8):73(abstract).
118. Restagno G, Romero N, Richard I, Beckmann JS, Pagliano AM, Ferrone M, et al. Prenatal diagnosis of limb girdle muscular dystrophy type 2A. Neuromuscul Disord 1996;6:173-176.