From the Department of Neurology IV (L. Maggi, G.B., D.K., P.B., L.C., R.M., L. Morandi), Neuromuscular Diseases and Neuroimmunology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Unit of Neuromuscular and Neurodegenerative Disorders (A.D., L.T., E.B.), Department of Neurosciences, IRCCS Bambino Gesù Children's Hospital, Rome; Child Neurology Unit (A.P.), IRCCS Institute of Neurological Sciences, Bologna; Department of Paediatric Neurology (S. Sivo, M.P., E.M.), Catholic University, Rome; Department of Clinical and Experimental Medicine (G.R., G.S.), Section of Neurology, University of Pisa; Department of Neuroscience Rita Levi Montalcini (L.V., T.M.), University of Torino; Cardiomyology and Medical Genetics (P.D., L.P.), Second Naples University; Arrhythmia Unit and Electrophysiology Laboratories (S. Sala), Institute of Experimental Neurology (Inspe) and Department of Neurology (M.S., S.C.P.) and Genomic Unit for the Diagnosis of Human Pathologies, Center for Translational Genomics and Bioinformatics (M.F.), San Raffaele Scientific Institute, Milan; Vita-Salute San Raffaele University (M.F.), Milan; Laboratory of Molecular Biology (M.F., S.B.), Diagnostica e Ricerca San Raffaele, Milan; Department of Neurosciences (E.P.), University of Padova, Padua; Department of Neurosciences (A.T., C.R.), University of Messina; National Research Council of Italy (G.L.), Institute of Molecular Genetics Unit of Bologna and Laboratory of Musculoskeletal Cell Biology IOR, Bologna; and Department of Public Health, Clinical and Molecular Medicine (N.C.), University of Cagliari, Italy.
Neurology. 2014 Oct 28;83(18):1634-44. doi: 10.1212/WNL.0000000000000934. Epub 2014 Oct 1.
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.
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.
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).
Our data provided new insights in LMNA-related myopathies, whose natural history appears to be dominated by cardiac involvement and related complications.
我们旨在对携带 LMNA 基因突变的肌病患者进行大样本的对比研究，以评估与不同表型相关的临床和分子特征。
我们对 78 例携带 LMNA 基因突变的肌病患者和 30 例无肌肉受累的家族性 LMNA 基因突变患者进行了回顾性队列研究。我们通过相关性统计分析了各种形式的 LMNA 相关性肌病的特征。
在 78 例患者中，37 例（47%）为肢带型肌营养不良 1B（LGMD1B），18 例（23%）为先天性肌营养不良（MDCL），17 例（22%）为常染色体显性遗传的 Emery-Dreifuss 肌营养不良 2 型（EDMD2），6 例（8%）为非典型肌病。肌病表型具有相似的心脏损害。与无肌肉受累的 30 例家族性病例相比，在 41 例肌病患者（53%）中植入了心脏除颤器或起搏器（p = 0.005）。心脏移植在 8 例肌病患者（10.3%）中进行，而在家族性病例中无 1 例（p = 0.032）。10 例（12.8%）肌病患者死亡，家族性病例中无死亡（p = 0.032）。14 例（82%）EDMD2 患者和 14 例（78%）MDCL 患者发现错义突变，而 17 例（45%）LGMD1B 患者和 4 例（67%）非典型患者发现错义突变。17 例（45%）LGMD1B 患者检测到移码突变，而 3 例（18%）EDMD2、1 例（6%）MDCL 和 2 例（33%）非典型患者发现移码突变（p = 0.021）。此外，在 30 例有心脏受累的 73 例患者（41%）中发现移码突变，而在 35 例无心脏受累的患者（11%）中发现 4 例（p = 0.004）。
我们的数据为 LMNA 相关性肌病提供了新的见解，其自然史似乎主要由心脏受累和相关并发症决定。
