LMNA-associated myopathies The Italian experience in a large cohort of patients

被引：51

作者：

Maggi, Lorenzo ^{[1
]}

D'Amico, Adele ^{[2
]}

Pini, Antonella ^{[3
]}

Sivo, Serena ^{[4
]}

Pane, Marika ^{[4
]}

Ricci, Giulia ^{[5
]}

Vercelli, Liliana ^{[6
]}

D'Ambrosio, Paola ^{[7
]}

Travaglini, Lorena ^{[2
]}

Sala, Simone ^{[8
,9
]}

Brenna, Greta ^{[1
]}

Kapetis, Dimos ^{[1
]}

Scarlato, Marina ^{[10
]}

Pegoraro, Elena ^{[14
]}

Ferrari, Maurizio ^{[11
,12
,13
]}

Toscano, Antonio ^{[15
]}

Benedetti, Sara ^{[13
]}

Bernasconi, Pia ^{[1
]}

Colleoni, Lara ^{[1
]}

Lattanzi, Giovanna ^{[16
,17
]}

Bertini, Enrico ^{[2
]}

Mercuri, Eugenio ^{[4
]}

Siciliano, Gabriele ^{[5
]}

Rodolico, Carmelo ^{[15
]}

Mongini, Tiziana ^{[6
]}

Politano, Luisa ^{[7
]}

Previtali, Stefano C. ^{[10
]}

Carboni, Nicola ^{[18
]}

Mantegazza, Renato ^{[1
]}

Morandi, Lucia ^{[1
]}

机构：

[1] Fdn IRCCS Ist Neurol Carlo Besta, Dept Neurol 4, Milan, Italy

[2] IRCCS Bambino Gesu Childrens Hosp, Unit Neuromuscular & Neurodegenerat Disorders, Dept Neurosci, Rome, Italy

[3] IRCCS Inst Neurol Sci, Child Neurol Unit, Bologna, Italy

[4] Catholic Univ, Dept Paediat Neurol, Rome, Italy

[5] Univ Pisa, Dept Clin & Expt Med, Neurol Sect, I-56100 Pisa, Italy

[6] Univ Turin, Dept Neurosci Rita Levi Montalcini, I-10124 Turin, Italy

[7] Univ Naples 2, Naples, Italy

[8] Ist Sci San Raffaele, Arrhythmia Unit, Inst Expt Neurol Inspe, I-20132 Milan, Italy

[9] Ist Sci San Raffaele, Electrophysiol Labs, Inst Expt Neurol Inspe, I-20132 Milan, Italy

[10] Ist Sci San Raffaele, Dept Neurol, I-20132 Milan, Italy

[11] Ist Sci San Raffaele, Genom Unit Diag Human Pathol, Ctr Translat Genom & Bioinformat, I-20132 Milan, Italy

[12] Univ Vita Salute San Raffaele, Milan, Italy

[13] Diagnost & Ric San Raffaele, Mol Biol Lab, Milan, Italy

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

[15] Univ Messina, Dept Neurosci, I-98100 Messina, Italy

[16] Natl Res Council Italy, Inst Mol Genet Unit Bologna, Bologna, Italy

[17] Lab Musculoskeletal Cell Biol IOR, Bologna, Italy

[18] Univ Cagliari, Dept Publ Hlth Clin & Mol Med, I-09124 Cagliari, Italy

来源：

NEUROLOGY | 2014年 / 83卷 / 18期

关键词：

LAMIN A/C GENE; GIRDLE MUSCULAR-DYSTROPHY; DILATED CARDIOMYOPATHY; FUNCTIONAL CONSEQUENCES; NUCLEAR LAMINS; MUTATIONS; LAMINOPATHIES; PHENOTYPE; FORM; INVOLVEMENT;

D O I：

10.1212/WNL.0000000000000934

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

100204 [神经病学];

摘要：

Objectives: Our aim was to conduct a comparative study in a large cohort of myopathic patients carrying LMNA gene mutations to evaluate clinical and molecular features associated with different phenotypes. Methods: We performed a retrospective cohort study of 78 myopathic patients with LMNA mutation and 30 familial cases with LMNA mutation without muscle involvement. We analyzed features characterizing the various forms of LMNA-related myopathy through correlation statistics. Results: Of the 78 patients, 37 (47%) had limb-girdle muscular dystrophy 1B (LGMD1B), 18 (23%) congenital muscular dystrophy (MDCL), 17 (22%) autosomal dominant Emery-Dreifuss muscular dystrophy 2 (EDMD2), and 6 (8%) an atypical myopathy. The myopathic phenotypes shared a similar cardiac impairment. Cardioverter defibrillator or pacemaker was implanted in 41 (53%) myopathic patients compared to 7 (23%) familial cases without muscle involvement (p = 0.005). Heart transplantation was performed in 8 (10.3%) myopathic patients and in none of the familial cases. Ten (12.8%) myopathic patients died; there were no deaths among the familial cases (p = 0.032). Missense mutations were found in 14 patients (82%) with EDMD2 and 14 patients (78%) with MDCL compared to 17 patients (45%) with LGMD1B and 4 (67%) atypical patients. Frameshift mutations were detected in 17 (45%) LGMD1B compared to 3 (18%) EDMD2, 1 (6%) MDCL, and 2 (33%) with atypical myopathy (p = 0.021). Furthermore, frameshift mutations were found in 30 of 73 patients (41%) with heart involvement compared to 4 of 35 (11%) without heart involvement (p = 0.004). Conclusions: Our data provided new insights in LMNA-related myopathies, whose natural history appears to be dominated by cardiac involvement and related complications.

引用

页码：1634 / 1644

页数：11

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