New genotype-phenotype correlations in a large European cohort of patients with sarcoglycanopathy

被引：51

作者：

Alonso-Perez, Jorge ^{[1
]}

Gonzalez-Quereda, Lidia ^{[2
,3
]}

Bello, Luca ^{[4
]}

Guglieri, Michela ^{[5
,6
]}

Straub, Volker ^{[5
,6
]}

Gallano, Pia ^{[2
,3
]}

Semplicini, Claudio ^{[4
]}

Pegoraro, Elena ^{[4
]}

Zangaro, Vittoria ^{[4
]}

Nascimento, Andres ^{[7
]}

Ortez, Carlos ^{[7
]}

Comi, Giacomo Pietro ^{[8
]}

ten Dam, Leroy ^{[9
]}

De Visser, Marianne ^{[9
]}

van der Kooi, A. J. ^{[9
]}

Garrido, Cristina ^{[10
]}

Santos, Manuela ^{[10
]}

Schara, Ulrike ^{[11
]}

Gangfuss, Andrea ^{[11
]}

Lokken, Nicoline ^{[12
,13
]}

Storgaard, Glesper Helbo ^{[12
,13
]}

Vissing, John ^{[12
,13
]}

Schoser, Benedikt ^{[14
]}

Dekomien, Gabriele ^{[15
]}

Udd, Bjarne ^{[16
,17
]}

Palmio, Johanna ^{[16
,17
]}

D'Amico, Adele ^{[18
]}

Politano, Luisa ^{[19
]}

Nigro, Vincenzo ^{[20
]}

Bruno, Claudio ^{[21
]}

Panicucci, Chiara ^{[21
]}

Sarkozy, Anna ^{[22
]}

Abdel-Mannan, Omar ^{[22
]}

Alonsolimenez, Alicia ^{[23
]}

Claeys, Kristl G. ^{[24
,25
]}

Gomez-Andres, David ^{[26
,27
]}

Munell, Francina ^{[26
,27
]}

Costa-Comellas, Laura ^{[26
,27
]}

Haberlova, Jana ^{[28
]}

Rohlenova, Marie ^{[28
]}

Elke, De Vos ^{[29
,30
]}

De Bleecker, Jan L. ^{[29
,30
]}

Dominguez-Gonzalez, Cristina ^{[4
,31
]}

Tasca, Giorgio ^{[32
]}

Weiss, Claudia ^{[33
]}

Deconinck, Nicolas ^{[34
]}

Fernandez-Torron, Roberto ^{[35
]}

de Munain, Adolfo Lopez ^{[35
]}

Camacho-Salas, Ana ^{[36
]}

Melegh, Bela ^{[37
,38
]}

机构：

[1] Univ Autonoma Barcelona, Dept Neurol, Neuromuscular Dis Unit, Hosp Santa Creu & St Pau, Barcelona, Spain

[2] Univ Autonoma Barcelona, Genet Dept, U705 CIBERER, Hosp Santa Creu & St Pau, Barcelona, Spain

[3] Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain

[4] Univ Padua, Dept Neurosci, Padua, Italy

[5] Newcastle Univ, John Walton Muscular Dystrophy Res Ctr, Newcastle Upon Tyne, Tyne & Wear, England

[6] Newcastle Hosp NHS Fdn Trust, Newcastle Upon Tyne, Tyne & Wear, England

[7] Hosp St Joan de Deu, Neuromuscular Disorder Unit, Barcelona, Spain

[8] Univ Milan, Fdn IRCCS Ca Granda Osped Maggiore Policlin, Dino Ferrari Ctr, Milan, Italy

[9] Univ Amsterdam, Dept Neurol, Amsterdam Neurosci, Amsterdam UMC, Amsterdam, Netherlands

[10] Ctr Hosp Porto, Neuropediat Dept, Porto, Portugal

[11] Univ Hosp Essen, Neuromuscular Ctr Children & Adolescents, Dept Paediat Neurol, Essen, Germany

[12] Rigshosp, Copenhagen Neuromuscular Ctr, Dept Neurol, Copenhagen, Denmark

[13] Univ Copenhagen, Copenhagen, Denmark

[14] Ludwig Maximilians Univ Munchen, Friedrich Baur Inst, Klinikum Munchen, Dept Neurol, Munich, Germany

[15] Ruhr Univ Bochum, Dept Human Genet, Bochum, Germany

[16] Univ Tampere, Neuromuscular Res Ctr, Tampere, Finland

[17] Tampere Univ Hosp, Tampere, Finland

[18] Bambino Gesu Pediat Hosp, Dept Neurosci, Unit Neuromuscular & Neurodegenerat Dis, Rome, Italy

[19] Univ Campania, Dept Expt Med, Cardiomiol & Med Genet, Naples, Italy

[20] Univ Campania, Dept Precis Med, Naples, Italy

[21] IRCCS, Ctr Translat & Expt Myol, Ist Giannina Gaslini, Genoa, Italy

[22] UCL Great Ormond St Inst Child Hlth, MRC Ctr Neuromuscular Dis, Dubowitz Neuromuscular Ctr, London, England

[23] Antwerp Univ Hosp, Neuromuscular Reference Ctr, Dept Neurol, Antwerp, Belgium

[24] Katholieke Univ Leuven, Dept Neurol, Univ Hosp Leuven, Leuven, Belgium

[25] Katholieke Univ Leuven, Lab Muscle Dis & Neuropathies, Dept Neurosci, Leuven, Belgium

[26] Vall dHebron Univ Hosp, Paediat Neuromuscular Disorders Unit, Pediat Neurol, Barcelona, Spain

[27] Vall dHebron Inst Res VHIR, Barcelona, Spain

[28] Charles Univ Prague, Univ Hosp Motol, Med Sch 2, Dept Child Neurol, Prague, Czech Republic

[29] Univ Ghent, Dept Neurol, Ghent, Belgium

[30] Univ Hosp Ghent, Ghent, Belgium

[31] Hosp Univ 12 Octubre, Inst Invest Imas12, Dept Neurol, Neuromuscular Unit, Madrid, Spain

[32] Fdn Policlin Univ A Gemelli IRCCS, UOC Neurol, Rome, Italy

[33] Charite Univ Med Berlin, Dept Neuropediat, Berlin, Germany

[34] Free Univ Brussels, Queen Fabiola Childrens Univ Hosp HUDERF, Dept Neurol, Brussels, Belgium

[35] Hosp Donostia, BioDonostia Hlth Res Inst, Neurosci, San Sebastian, Spain

[36] Univ Complutense Madrid, Hosp Univ 12 Octubre, Div Child Neurol, Madrid, Spain

[37] Univ Pecs, Sch Med, Dept Med Genet, Pecs, Hungary

[38] Univ Pecs, Szentagothai Res Ctr, Sch Med, Pecs, Hungary

[39] Univ Ljubljana, Univ Med Ctr, Fac Med, Inst Clin Neurophysiol,Dept Neurol, Ljubljana, Slovenia

[40] SAPIENZA Univ Roma, Dept Neurosci Mental Hlth & Sensory Organs NESMOS, Neuromuscular & Rare Dis Ctr, Rome, Italy

[41] Hosp Univ Nuestra Senora Candelaria, Dept Neurol, Tenerife, Spain

[42] Raymond Poincare Teaching Hosp, AP HP, Dept Neurol, Ctr Reference Malad Neuromusculaires Nord Est Ile, Garches, France

[43] Alvaro Cunqueiro Hosp, Dept Neurol, Vigo, Spain

[44] Univ Paris Saclay, Univ Evry, Genethon, Integrare UMR 5951,INSERM, F-91002 Evry, France

来源：

BRAIN | 2020年 / 143卷

关键词：

limb girdle muscular dystrophies; sarcoglycan; registries; treatment; cohort; GIRDLE MUSCULAR-DYSTROPHY; HEART INVOLVEMENT; COMPLEX; SPECTRUM; MUTATIONS; DIAGNOSIS;

D O I：

10.1093/brain/awaa228

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Sarcoglycanopathies comprise four subtypes of autosomal recessive limb-girdle muscular dystrophies (LGMDR3, LGMDR4, LGMDR5 and LGMDR6) that are caused, respectively, by mutations in the SGCA, SGCB, SGCG and SGCD genes. In 2016, several clinicians involved in the diagnosis, management and care of patients with LGMDR3-6 created a European Sarcoglycanopathy Consortium. The aim of the present study was to determine the clinical and genetic spectrum of a large cohort of patients with sarcoglycanopathy in Europe. This was an observational retrospective study. A total of 33 neuromuscular centres from 13 different European countries collected data of the genetically confirmed patients with sarcoglycanopathy followed-up at their centres. Demographic, genetic and clinical data were collected for this study. Data from 439 patients from 13 different countries were collected. Forty-three patients were not included in the analysis because of insufficient clinical information available. A total of 159 patients had a confirmed diagnosis of LGMDR3, 73 of LGMDR4, 157 of LGMDR5 and seven of LGMDR6. Patients with LGMDR3 had a later onset and slower progression of the disease. Cardiac involvement was most frequent in LGMDR4. Sixty per cent of LGMDR3 patients carried one of the following mutations, either in a homozygous or heterozygous state: Wc.229C>T, c.739G>A or c.850C>T. Similarly, the most common mutations in LMGDR5 patients were c.525delT or c.848G>A. In LGMDR4 patients the most frequent mutation was c.341C>T. We identified onset of symptoms before 10 years of age and residual protein expression lower than 30% as independent risk factors for losing ambulation before 18 years of age, in LGMDR3, LGMDR4 and LGMDR5 patients. This study reports clinical, genetic and protein data of a large European cohort of patients with sarcoglycanopathy. Improving our knowledge about these extremely rare autosomal recessive forms of LGMD was helped by a collaborative effort of neuromuscular centres across Europe. Our study provides important data on the genotype-phenotype correlation that is relevant for the design of natural history studies and upcoming interventional trials in sarcoglycanopathies.

引用

页码：2696 / 2708

页数：13

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