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

作者：Maggi Lorenzo^*; D' Amico Adele; Pini Antonella; Sivo Serena; Pane Marika; Ricci Giulia; Vercelli Liliana; D' Ambrosio Paola; Travaglini Lorena; Sala Simone; Brenna Greta; Kapetis Dimos; Scarlato Marina; Pegoraro Elena; Ferrari Maurizio; Toscano Antonio; Benedetti Sara; Bernasconi Pia; Colleoni Lara; Lattanzi Giovanna; Bertini Enrico; Mercuri Eugenio; Siciliano Gabriele; Rodolico Carmelo; Mongini Tiziana; Politano Luisa; Previtali Stefano C

来源：Neurology, 2014, 83(18): 1634-1644.

DOI：10.1212/WNL.0000000000000934

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. %26lt;br%26gt;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. %26lt;br%26gt;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). %26lt;br%26gt;Conclusions: Our data provided new insights in LMNA-related myopathies, whose natural history appears to be dominated by cardiac involvement and related complications.

• 出版日期2014-10-28