The italian limb girdle muscular dystrophy registry: Relative frequency, clinical features, and differential diagnosis

F. Magri, V. Nigro, C. Angelini, T. Mongini, M. Mora, I. Moroni, A. Toscano, M.G. D'angelo, G. Tomelleri, Gabriele Siciliano, G. Ricci, Claudio Bruno, S. Corti, Olimpia1 Musumeci, G. Tasca, E. Ricci, Mauro Monforte, M. Sciacco, C. Fiorillo, S. Gandossini & 13 others C. Minetti, L. Morandi, M. Savarese, Giuseppina Di Fruscio, Claudio Semplicini, E. Pegoraro, Alessandra Govoni, R. Brusa, R. Del Bo, D. Ronchi, M. Moggio, N. Bresolin, G.P. Comi

Research output: Contribution to journalArticle

Abstract

Introduction: Limb girdle muscular dystrophies (LGMDs) are characterized by high molecular heterogeneity, clinical overlap, and a paucity of specific biomarkers. Their molecular definition is fundamental for prognostic and therapeutic purposes. Methods: We created an Italian LGMD registry that included 370 molecularly defined patients. We reviewed detailed retrospective and prospective data and compared each LGMD subtype for differential diagnosis purposes. Results: LGMD types 2A and 2B are the most frequent forms in Italy. The ages at disease onset, clinical progression, and cardiac and respiratory involvement can vary greatly between each LGMD subtype. In a set of extensively studied patients, targeted next-generation sequencing (NGS) identified mutations in 36.5% of cases. Conclusion: Detailed clinical characterization combined with muscle tissue analysis is fundamental to guide differential diagnosis and to address molecular tests. NGS is useful for diagnosing forms without specific biomarkers, although, at least in our study cohort, several LGMD disease mechanisms remain to be identified. Muscle Nerve 55: 55–68, 2017. © 2016 Wiley Periodicals, Inc.
Original languageEnglish
Pages (from-to)55-68
Number of pages14
JournalMuscle and Nerve
Volume55
Issue number1
DOIs
Publication statusPublished - Oct 28 2016

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Limb-Girdle Muscular Dystrophies
Registries
Differential Diagnosis
Biomarkers
Muscles
Muscular Diseases
Age of Onset
Italy
Cohort Studies
Mutation

Keywords

  • differential diagnosis
  • genotype–phenotype correlations
  • limb girdle muscular dystrophy
  • natural history
  • next-generation sequencing

Cite this

Magri, F., Nigro, V., Angelini, C., Mongini, T., Mora, M., Moroni, I., ... Comi, G. P. (2016). The italian limb girdle muscular dystrophy registry: Relative frequency, clinical features, and differential diagnosis. Muscle and Nerve, 55(1), 55-68. https://doi.org/10.1002/mus.25192

The italian limb girdle muscular dystrophy registry: Relative frequency, clinical features, and differential diagnosis. / Magri, F.; Nigro, V.; Angelini, C.; Mongini, T.; Mora, M.; Moroni, I.; Toscano, A.; D'angelo, M.G.; Tomelleri, G.; Siciliano, Gabriele; Ricci, G.; Bruno, Claudio; Corti, S.; Musumeci, Olimpia1; Tasca, G.; Ricci, E.; Monforte, Mauro; Sciacco, M.; Fiorillo, C.; Gandossini, S.; Minetti, C.; Morandi, L.; Savarese, M.; Di Fruscio, Giuseppina; Semplicini, Claudio; Pegoraro, E.; Govoni, Alessandra; Brusa, R.; Del Bo, R.; Ronchi, D.; Moggio, M.; Bresolin, N.; Comi, G.P.

In: Muscle and Nerve, Vol. 55, No. 1, 28.10.2016, p. 55-68.

Research output: Contribution to journalArticle

Magri, F, Nigro, V, Angelini, C, Mongini, T, Mora, M, Moroni, I, Toscano, A, D'angelo, MG, Tomelleri, G, Siciliano, G, Ricci, G, Bruno, C, Corti, S, Musumeci, O, Tasca, G, Ricci, E, Monforte, M, Sciacco, M, Fiorillo, C, Gandossini, S, Minetti, C, Morandi, L, Savarese, M, Di Fruscio, G, Semplicini, C, Pegoraro, E, Govoni, A, Brusa, R, Del Bo, R, Ronchi, D, Moggio, M, Bresolin, N & Comi, GP 2016, 'The italian limb girdle muscular dystrophy registry: Relative frequency, clinical features, and differential diagnosis', Muscle and Nerve, vol. 55, no. 1, pp. 55-68. https://doi.org/10.1002/mus.25192
Magri, F. ; Nigro, V. ; Angelini, C. ; Mongini, T. ; Mora, M. ; Moroni, I. ; Toscano, A. ; D'angelo, M.G. ; Tomelleri, G. ; Siciliano, Gabriele ; Ricci, G. ; Bruno, Claudio ; Corti, S. ; Musumeci, Olimpia1 ; Tasca, G. ; Ricci, E. ; Monforte, Mauro ; Sciacco, M. ; Fiorillo, C. ; Gandossini, S. ; Minetti, C. ; Morandi, L. ; Savarese, M. ; Di Fruscio, Giuseppina ; Semplicini, Claudio ; Pegoraro, E. ; Govoni, Alessandra ; Brusa, R. ; Del Bo, R. ; Ronchi, D. ; Moggio, M. ; Bresolin, N. ; Comi, G.P. / The italian limb girdle muscular dystrophy registry: Relative frequency, clinical features, and differential diagnosis. In: Muscle and Nerve. 2016 ; Vol. 55, No. 1. pp. 55-68.
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abstract = "Introduction: Limb girdle muscular dystrophies (LGMDs) are characterized by high molecular heterogeneity, clinical overlap, and a paucity of specific biomarkers. Their molecular definition is fundamental for prognostic and therapeutic purposes. Methods: We created an Italian LGMD registry that included 370 molecularly defined patients. We reviewed detailed retrospective and prospective data and compared each LGMD subtype for differential diagnosis purposes. Results: LGMD types 2A and 2B are the most frequent forms in Italy. The ages at disease onset, clinical progression, and cardiac and respiratory involvement can vary greatly between each LGMD subtype. In a set of extensively studied patients, targeted next-generation sequencing (NGS) identified mutations in 36.5{\%} of cases. Conclusion: Detailed clinical characterization combined with muscle tissue analysis is fundamental to guide differential diagnosis and to address molecular tests. NGS is useful for diagnosing forms without specific biomarkers, although, at least in our study cohort, several LGMD disease mechanisms remain to be identified. Muscle Nerve 55: 55–68, 2017. {\circledC} 2016 Wiley Periodicals, Inc.",
keywords = "differential diagnosis, genotype–phenotype correlations, limb girdle muscular dystrophy, natural history, next-generation sequencing",
author = "F. Magri and V. Nigro and C. Angelini and T. Mongini and M. Mora and I. Moroni and A. Toscano and M.G. D'angelo and G. Tomelleri and Gabriele Siciliano and G. Ricci and Claudio Bruno and S. Corti and Olimpia1 Musumeci and G. Tasca and E. Ricci and Mauro Monforte and M. Sciacco and C. Fiorillo and S. Gandossini and C. Minetti and L. Morandi and M. Savarese and {Di Fruscio}, Giuseppina and Claudio Semplicini and E. Pegoraro and Alessandra Govoni and R. Brusa and {Del Bo}, R. and D. Ronchi and M. Moggio and N. Bresolin and G.P. Comi",
note = "Export Date: 14 March 2017 CODEN: MUNED Correspondence Address: Comi, G.P.; Dino Ferrari Centre, Department of Pathophysiology and Transplantation, University of Milan, Neurology Unit, IRCCS Foundation Ca' Granda, Ospedale Maggiore Policlinico, Via Francesco Sforza 35, Italy; email: giacomo.comi@unimi.it References: Walton, J.N., Nattrass, F.J., On the classification, natural history and treatment of the myopathies (1954) Brain, 77, pp. 170-231; Beckmann, J.S., Disease taxonomy—monogenic muscular dystrophy (1999) Br Med Bull, 55, pp. 340-357; Norwood, F.L., Harling, C., Chinnery, P.F., Eagle, M., Bushby, K., Straub, V., Prevalence of genetic muscle disease in northern England: in-depth analysis of a muscle clinic population (2009) Brain, 132, pp. 3175-3186; Magri, F., Brajkovic, S., Govoni, A., Brusa, R., Comi, G.P., Revised genetic classification of limb girdle muscular dystrophies (2014) Curr Mol Med, 14, pp. 934-943; Nigro, V., Savarese, M., Genetic basis of limb-girdle muscular dystrophies: the 2014 update (2014) Acta Myol, 33, pp. 1-12; Narayanaswami, P., Weiss, M., Selcen, D., David, W., Raynor, E., Carter, G., Guideline Development Subcommittee of the American Academy of Neurology; Practice Issues Review Panel of the American Association of Neuromuscular & Electrodiagnostic Medicine. Evidence-based guideline summary: diagnosis and treatment of limb-girdle and distal dystrophies: report of the guideline development subcommittee of the American Academy of Neurology and the practice issues review panel of the American Association of Neuromuscular & Electrodiagnostic Medicine (2014) Neurology, 83, pp. 1453-1463; Murphy, A.P., Straub, V., The classification, natural history and treatment of limb girdle muscular dystrophies (2015) J Neuromuscul Dis, 2, pp. S7-S19; Norwood, F., de Visser, M., Eymard, B., Lochm{\"u}ller, H., Bushby, K., EFNS guideline on diagnosis and management of limb girdle muscular dystrophies (2007) Eur J Neurol, 12, pp. 1305-1312; Guglieri, M., Straub, V., Bushby, K., Lochm{\"u}ller, H., Limb-girdle muscular dystrophies (2008) Curr Opin Neurol, 5, pp. 576-584; Sarparanta, J., Jonson, P.H., Golzio, C., Sandell, S., Luque, H., Screen, M., Mutations affecting the cytoplasmic functions of the co-chaperone DNAJB6 cause limb-girdle muscular dystrophy (2012) Nat Genet, 44, pp. 450-455. , S1–2; Vieira, N.M., Naslavsky, M.S., Licinio, L., Kok, F., Schlesinger, D., Vainzof, M., A defect in the RNA-processing protein HNRPDL causes limb-girdle muscular dystrophy 1G (LGMD1G) (2014) Hum Mol Genet, 23, pp. 4103-4110; Torella, A., Fanin, M., Mutarelli, M., Peterle, E., Del Vecchio Blanco, F., Rispoli, R., Next-generation sequencing identifies transportin 3 as the causative gene for LGMD1F (2013) PLoS One, 8; Nectoux, J., de Cid, R., Baulande, S., Leturcq, F., Urtizberea, J.A., Penisson-Besnier, I., Detection of TRIM32 deletions in LGMD patients analyzed by a combined strategy of CGH array and massively parallel sequencing (2015) Eur J Hum Genet, 23, pp. 929-934; Carss, K.J., Stevens, E., Foley, A.R., Cirak, S., Riemersma, M., Torelli, S., Mutations in GDP-mannose pyrophosphorylase B cause congenital and limb-girdle muscular dystrophies associated with hypoglycosylation of α-dystroglycan (2013) Am J Hum Genet, 93, pp. 29-41; Tasca, G., Moro, F., Aiello, C., Cassandrini, D., Fiorillo, C., Bertini, E., Limb-girdle muscular dystrophy with α-dystroglycan deficiency and mutations in the ISPD gene (2013) Neurology, 80, pp. 963-965; Bushby, K., Diagnosis and management of the limb girdle muscular dystrophies (2009) Pract Neurol, 9, pp. 314-323; Walton, J.N., Gardner-Medwin, D., Progressive muscular dystrophy and the myotonic disorders (1981) Disorders of voluntary muscle, pp. 481-524. , In, Walton JN, editor., 4th ed, Edinburgh, Churchill Livingstone, p; Dubowitz, V., Sewry, C.A., Lane, R.J.M., (2007) Muscle biopsy: a practical approach, , 3rd ed, Philadelphia, Saunders Elsevier; Nicholson, L.V., Davison, K., Johnson, M.A., Slater, C.R., Young, C., Bhattacharya, S., Dystrophin in skeletal muscle. Immunoreactivity in patients with Xp21 muscular dystrophy (1989) J Neurol Sci, 94, pp. 137-146; Prelle, A., Comi, G.P., Tancredi, L., Rigoletto, C., Ciscato, P., Fortunato, F., Sarcoglycan deficiency in a large Italian population of myopathic patients (1998) Acta Neuropathol, 96, pp. 509-514; Anderson, L.V., Davison, K., Moss, J.A., Richard, I., Fardeau, M., Tom{\'e}, F.M., Characterization of monoclonal antibodies to calpain 3 and protein expression in muscle from patients with limb-girdle muscular dystrophy type 2A (1998) Am J Pathol, 153, pp. 1169-1179; Savarese, M., Di Fruscio, G., Mutarelli, M., Torella, A., Magri, F., Santorelli, F.M., MotorPlex provides accurate variant detection across large muscle genes both in single myopathic patients and in pools of DNA samples (2014) Acta Neuropathol Commun, 2, p. 100; Frosk, P., Greenberg, C.R., Tennese, A.A., Lamont, R., Nylen, E., Hirst, C., The most common mutation in FKRP causing limb girdle muscular dystrophy type 2I (LGMD2I) may have occurred only once and is present in Hutterites and other populations (2005) Hum Mutat, 25, pp. 38-44; Zatz, M., Starling, A., Calpains and disease (2005) N Engl J Med, 352, pp. 2413-2423; Fanin, M., Nascimbeni, A.C., Aurino, S., Tasca, E., Pegoraro, E., Nigro, V., Frequency of LGMD gene mutations in Italian patients with distinct clinical phenotypes (2009) Neurology, 72, pp. 1432-1435; Van der Kooi, A.J., Barth, P.G., Busch, H.F., de Haan, R., Ginjaar, H.B., van Essen, A.J., The clinical spectrum of limb girdle muscular dystrophy. A survey in The Netherlands (1996) Brain, 119, pp. 1471-1480; Topaloğlu, H., Din{\cc}er, P., Richard, I., Ak{\cc}{\"o}ren, Z., Alehan, D., Ozme, S., Calpain-3 deficiency causes a mild muscular dystrophy in childhood (1997) Neuropediatrics, 28, pp. 212-216; Urtasun, M., S{\'a}enz, A., Roudaut, C., Poza, J.J., Urtizberea, J.A., Cobo, A.M., Limb-girdle muscular dystrophy in Guip{\'u}zcoa (Basque Country, Spain) (1998) Brain, 121, pp. 1735-1747; Passos-Bueno, M.R., Vainzof, M., Moreira, E.S., Zatz, M., Seven autosomal recessive limb-girdle muscular dystrophies in the Brazilian population: from LGMD2A to LGMD2G (1999) Am J Med Genet, 82, pp. 392-398; Pogoda, T.V., Krakhmaleva, I.N., Lipatova, N.A., Shakhovskaya, N.I., Shishkin, S.S., Limborska, S.A., High incidence of 550delA mutation of CAPN3 in LGMD2 patients from Russia (2000) Hum Mutat, 15, p. 295; Chae, J., Minami, N., Jin, Y., Nakagawa, M., Murayama, K., Igarashi, F., Calpain 3 gene mutations: genetic and clinico-pathologic findings in limb-girdle muscular dystrophy (2001) Neuromuscul Disord, 11, pp. 547-555; Sveen, M.L., Schwartz, M., Vissing, J., High prevalence and phenotype-genotype correlations of limb girdle muscular dystrophy type 2I in Denmark (2006) Ann Neurol, 59, pp. 808-815; Witting, N., Duno, M., Petri, H., Krag, T., Bundgaard, H., Kober, L., Anoctamin 5 muscular dystrophy in Denmark: prevalence, genotypes, phenotypes, cardiac findings, and muscle protein expression (2013) J Neurol, 260, pp. 2084-2093; Tan, E., Topaloglu, H., Sewry, C., Zorlu, Y., Naom, I., Erdem, S., Late onset muscular dystrophy with cerebral white matter changes due to partial merosin deficiency (1997) Neuromuscul Disord, 7, pp. 85-89",
year = "2016",
month = "10",
day = "28",
doi = "10.1002/mus.25192",
language = "English",
volume = "55",
pages = "55--68",
journal = "Muscle and Nerve",
issn = "0148-639X",
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}

TY - JOUR

T1 - The italian limb girdle muscular dystrophy registry: Relative frequency, clinical features, and differential diagnosis

AU - Magri, F.

AU - Nigro, V.

AU - Angelini, C.

AU - Mongini, T.

AU - Mora, M.

AU - Moroni, I.

AU - Toscano, A.

AU - D'angelo, M.G.

AU - Tomelleri, G.

AU - Siciliano, Gabriele

AU - Ricci, G.

AU - Bruno, Claudio

AU - Corti, S.

AU - Musumeci, Olimpia1

AU - Tasca, G.

AU - Ricci, E.

AU - Monforte, Mauro

AU - Sciacco, M.

AU - Fiorillo, C.

AU - Gandossini, S.

AU - Minetti, C.

AU - Morandi, L.

AU - Savarese, M.

AU - Di Fruscio, Giuseppina

AU - Semplicini, Claudio

AU - Pegoraro, E.

AU - Govoni, Alessandra

AU - Brusa, R.

AU - Del Bo, R.

AU - Ronchi, D.

AU - Moggio, M.

AU - Bresolin, N.

AU - Comi, G.P.

N1 - Export Date: 14 March 2017 CODEN: MUNED Correspondence Address: Comi, G.P.; Dino Ferrari Centre, Department of Pathophysiology and Transplantation, University of Milan, Neurology Unit, IRCCS Foundation Ca' Granda, Ospedale Maggiore Policlinico, Via Francesco Sforza 35, Italy; email: giacomo.comi@unimi.it References: Walton, J.N., Nattrass, F.J., On the classification, natural history and treatment of the myopathies (1954) Brain, 77, pp. 170-231; Beckmann, J.S., Disease taxonomy—monogenic muscular dystrophy (1999) Br Med Bull, 55, pp. 340-357; Norwood, F.L., Harling, C., Chinnery, P.F., Eagle, M., Bushby, K., Straub, V., Prevalence of genetic muscle disease in northern England: in-depth analysis of a muscle clinic population (2009) Brain, 132, pp. 3175-3186; Magri, F., Brajkovic, S., Govoni, A., Brusa, R., Comi, G.P., Revised genetic classification of limb girdle muscular dystrophies (2014) Curr Mol Med, 14, pp. 934-943; Nigro, V., Savarese, M., Genetic basis of limb-girdle muscular dystrophies: the 2014 update (2014) Acta Myol, 33, pp. 1-12; Narayanaswami, P., Weiss, M., Selcen, D., David, W., Raynor, E., Carter, G., Guideline Development Subcommittee of the American Academy of Neurology; Practice Issues Review Panel of the American Association of Neuromuscular & Electrodiagnostic Medicine. Evidence-based guideline summary: diagnosis and treatment of limb-girdle and distal dystrophies: report of the guideline development subcommittee of the American Academy of Neurology and the practice issues review panel of the American Association of Neuromuscular & Electrodiagnostic Medicine (2014) Neurology, 83, pp. 1453-1463; Murphy, A.P., Straub, V., The classification, natural history and treatment of limb girdle muscular dystrophies (2015) J Neuromuscul Dis, 2, pp. S7-S19; Norwood, F., de Visser, M., Eymard, B., Lochmüller, H., Bushby, K., EFNS guideline on diagnosis and management of limb girdle muscular dystrophies (2007) Eur J Neurol, 12, pp. 1305-1312; Guglieri, M., Straub, V., Bushby, K., Lochmüller, H., Limb-girdle muscular dystrophies (2008) Curr Opin Neurol, 5, pp. 576-584; Sarparanta, J., Jonson, P.H., Golzio, C., Sandell, S., Luque, H., Screen, M., Mutations affecting the cytoplasmic functions of the co-chaperone DNAJB6 cause limb-girdle muscular dystrophy (2012) Nat Genet, 44, pp. 450-455. , S1–2; Vieira, N.M., Naslavsky, M.S., Licinio, L., Kok, F., Schlesinger, D., Vainzof, M., A defect in the RNA-processing protein HNRPDL causes limb-girdle muscular dystrophy 1G (LGMD1G) (2014) Hum Mol Genet, 23, pp. 4103-4110; Torella, A., Fanin, M., Mutarelli, M., Peterle, E., Del Vecchio Blanco, F., Rispoli, R., Next-generation sequencing identifies transportin 3 as the causative gene for LGMD1F (2013) PLoS One, 8; Nectoux, J., de Cid, R., Baulande, S., Leturcq, F., Urtizberea, J.A., Penisson-Besnier, I., Detection of TRIM32 deletions in LGMD patients analyzed by a combined strategy of CGH array and massively parallel sequencing (2015) Eur J Hum Genet, 23, pp. 929-934; Carss, K.J., Stevens, E., Foley, A.R., Cirak, S., Riemersma, M., Torelli, S., Mutations in GDP-mannose pyrophosphorylase B cause congenital and limb-girdle muscular dystrophies associated with hypoglycosylation of α-dystroglycan (2013) Am J Hum Genet, 93, pp. 29-41; Tasca, G., Moro, F., Aiello, C., Cassandrini, D., Fiorillo, C., Bertini, E., Limb-girdle muscular dystrophy with α-dystroglycan deficiency and mutations in the ISPD gene (2013) Neurology, 80, pp. 963-965; Bushby, K., Diagnosis and management of the limb girdle muscular dystrophies (2009) Pract Neurol, 9, pp. 314-323; Walton, J.N., Gardner-Medwin, D., Progressive muscular dystrophy and the myotonic disorders (1981) Disorders of voluntary muscle, pp. 481-524. , In, Walton JN, editor., 4th ed, Edinburgh, Churchill Livingstone, p; Dubowitz, V., Sewry, C.A., Lane, R.J.M., (2007) Muscle biopsy: a practical approach, , 3rd ed, Philadelphia, Saunders Elsevier; Nicholson, L.V., Davison, K., Johnson, M.A., Slater, C.R., Young, C., Bhattacharya, S., Dystrophin in skeletal muscle. Immunoreactivity in patients with Xp21 muscular dystrophy (1989) J Neurol Sci, 94, pp. 137-146; Prelle, A., Comi, G.P., Tancredi, L., Rigoletto, C., Ciscato, P., Fortunato, F., Sarcoglycan deficiency in a large Italian population of myopathic patients (1998) Acta Neuropathol, 96, pp. 509-514; Anderson, L.V., Davison, K., Moss, J.A., Richard, I., Fardeau, M., Tomé, F.M., Characterization of monoclonal antibodies to calpain 3 and protein expression in muscle from patients with limb-girdle muscular dystrophy type 2A (1998) Am J Pathol, 153, pp. 1169-1179; Savarese, M., Di Fruscio, G., Mutarelli, M., Torella, A., Magri, F., Santorelli, F.M., MotorPlex provides accurate variant detection across large muscle genes both in single myopathic patients and in pools of DNA samples (2014) Acta Neuropathol Commun, 2, p. 100; Frosk, P., Greenberg, C.R., Tennese, A.A., Lamont, R., Nylen, E., Hirst, C., The most common mutation in FKRP causing limb girdle muscular dystrophy type 2I (LGMD2I) may have occurred only once and is present in Hutterites and other populations (2005) Hum Mutat, 25, pp. 38-44; Zatz, M., Starling, A., Calpains and disease (2005) N Engl J Med, 352, pp. 2413-2423; Fanin, M., Nascimbeni, A.C., Aurino, S., Tasca, E., Pegoraro, E., Nigro, V., Frequency of LGMD gene mutations in Italian patients with distinct clinical phenotypes (2009) Neurology, 72, pp. 1432-1435; Van der Kooi, A.J., Barth, P.G., Busch, H.F., de Haan, R., Ginjaar, H.B., van Essen, A.J., The clinical spectrum of limb girdle muscular dystrophy. A survey in The Netherlands (1996) Brain, 119, pp. 1471-1480; Topaloğlu, H., Dinçer, P., Richard, I., Akçören, Z., Alehan, D., Ozme, S., Calpain-3 deficiency causes a mild muscular dystrophy in childhood (1997) Neuropediatrics, 28, pp. 212-216; Urtasun, M., Sáenz, A., Roudaut, C., Poza, J.J., Urtizberea, J.A., Cobo, A.M., Limb-girdle muscular dystrophy in Guipúzcoa (Basque Country, Spain) (1998) Brain, 121, pp. 1735-1747; Passos-Bueno, M.R., Vainzof, M., Moreira, E.S., Zatz, M., Seven autosomal recessive limb-girdle muscular dystrophies in the Brazilian population: from LGMD2A to LGMD2G (1999) Am J Med Genet, 82, pp. 392-398; Pogoda, T.V., Krakhmaleva, I.N., Lipatova, N.A., Shakhovskaya, N.I., Shishkin, S.S., Limborska, S.A., High incidence of 550delA mutation of CAPN3 in LGMD2 patients from Russia (2000) Hum Mutat, 15, p. 295; Chae, J., Minami, N., Jin, Y., Nakagawa, M., Murayama, K., Igarashi, F., Calpain 3 gene mutations: genetic and clinico-pathologic findings in limb-girdle muscular dystrophy (2001) Neuromuscul Disord, 11, pp. 547-555; Sveen, M.L., Schwartz, M., Vissing, J., High prevalence and phenotype-genotype correlations of limb girdle muscular dystrophy type 2I in Denmark (2006) Ann Neurol, 59, pp. 808-815; Witting, N., Duno, M., Petri, H., Krag, T., Bundgaard, H., Kober, L., Anoctamin 5 muscular dystrophy in Denmark: prevalence, genotypes, phenotypes, cardiac findings, and muscle protein expression (2013) J Neurol, 260, pp. 2084-2093; Tan, E., Topaloglu, H., Sewry, C., Zorlu, Y., Naom, I., Erdem, S., Late onset muscular dystrophy with cerebral white matter changes due to partial merosin deficiency (1997) Neuromuscul Disord, 7, pp. 85-89

PY - 2016/10/28

Y1 - 2016/10/28

N2 - Introduction: Limb girdle muscular dystrophies (LGMDs) are characterized by high molecular heterogeneity, clinical overlap, and a paucity of specific biomarkers. Their molecular definition is fundamental for prognostic and therapeutic purposes. Methods: We created an Italian LGMD registry that included 370 molecularly defined patients. We reviewed detailed retrospective and prospective data and compared each LGMD subtype for differential diagnosis purposes. Results: LGMD types 2A and 2B are the most frequent forms in Italy. The ages at disease onset, clinical progression, and cardiac and respiratory involvement can vary greatly between each LGMD subtype. In a set of extensively studied patients, targeted next-generation sequencing (NGS) identified mutations in 36.5% of cases. Conclusion: Detailed clinical characterization combined with muscle tissue analysis is fundamental to guide differential diagnosis and to address molecular tests. NGS is useful for diagnosing forms without specific biomarkers, although, at least in our study cohort, several LGMD disease mechanisms remain to be identified. Muscle Nerve 55: 55–68, 2017. © 2016 Wiley Periodicals, Inc.

AB - Introduction: Limb girdle muscular dystrophies (LGMDs) are characterized by high molecular heterogeneity, clinical overlap, and a paucity of specific biomarkers. Their molecular definition is fundamental for prognostic and therapeutic purposes. Methods: We created an Italian LGMD registry that included 370 molecularly defined patients. We reviewed detailed retrospective and prospective data and compared each LGMD subtype for differential diagnosis purposes. Results: LGMD types 2A and 2B are the most frequent forms in Italy. The ages at disease onset, clinical progression, and cardiac and respiratory involvement can vary greatly between each LGMD subtype. In a set of extensively studied patients, targeted next-generation sequencing (NGS) identified mutations in 36.5% of cases. Conclusion: Detailed clinical characterization combined with muscle tissue analysis is fundamental to guide differential diagnosis and to address molecular tests. NGS is useful for diagnosing forms without specific biomarkers, although, at least in our study cohort, several LGMD disease mechanisms remain to be identified. Muscle Nerve 55: 55–68, 2017. © 2016 Wiley Periodicals, Inc.

KW - differential diagnosis

KW - genotype–phenotype correlations

KW - limb girdle muscular dystrophy

KW - natural history

KW - next-generation sequencing

U2 - 10.1002/mus.25192

DO - 10.1002/mus.25192

M3 - Article

VL - 55

SP - 55

EP - 68

JO - Muscle and Nerve

JF - Muscle and Nerve

SN - 0148-639X

IS - 1

ER -