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.

LMNA-associated myopathies: the Italian experience in a large cohort of patients.

VERCELLI, Liliana;MONGINI, Tiziana Enrica;
2014-01-01

Abstract

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.
2014
83
18
1634
1644
Maggi L;D'Amico A;Pini A;Sivo S;Pane M;Ricci G;Vercelli L;D'Ambrosio P;Travaglini L;Sala S;Brenna G;Kapetis D;Scarlato M;Pegoraro E;Ferrari M;Toscano ...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/153395
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