Petillo Roberta, D'Ambrosio Paola, Torella Annalaura, Taglia Antonella, Picillo Esther, Testori Alessandro, Ergoli Manuela, Nigro Gerardo, Piluso Giulio, Nigro Vincenzo, Politano Luisa
Cardiomyology and Medical Genetics, Department of Experimental Medicine;
Laboratory of Medical Genetics, Department of Biochemistry, Biophysics and General Pathology;
Acta Myol. 2015 Dec;34(2-3):116-9.
Mutations in the lamin A/C gene (LMNA) have been associated with several phenotypes ranging from systemic to prevalent of muscle, heart, skin, nerve etc. More recently they have been associated with dilated cardiomyopathy (DCM) and severe forms of arrhythmogenic right ventricular cardiomyopathy (ARVC). We report four novel mutations - 3 missense and 1 deletion - in 4 unrelated patients showing different phenotypes, ranging from the early onset congenital form of laminopathy to classical LGMD phenotype, to LGMD and heart involvement. All these newly identified variants were not found in 300 ethnicallymatched control subjects. The variant c.103-105del CTG was described post-mortem in a young patient with congenital muscular dystrophy who presented at the age of 9 a first degree A-V block and subsequently several episodes of supraventricular parossystic tachycardia. Two patients presented as onset symptom lower limbs muscle weakness, and developed heart conduction defects requiring pacemaker implantation at the age of 26 and 38 years, respectively. One of them who carried the mutation c.1339G>C died at the age of 40 by intractable heart failure; the second one carrying the mutation 265C>T died at the age of 30, for a trmboembolic event. A classical LGMD phenotype without heart involvement was observed in the patient with the mutation 1579C>T, who died at the age of 68 years for respiratory insufficiency.
核纤层蛋白A/C基因（LMNA）突变与多种表型相关，从全身性表型到肌肉、心脏、皮肤、神经等常见表型。最近，它们与扩张型心肌病（DCM）和致心律失常性右室心肌病（ARVC）的严重形式有关。我们报告了4例无亲缘关系患者中的4种新突变——3种错义突变和1种缺失突变，这些患者表现出不同的表型，从早发性先天性核纤层蛋白病形式到经典的肢带型肌营养不良（LGMD）表型，再到LGMD合并心脏受累。在300名种族匹配的对照受试者中未发现所有这些新鉴定的变异。变异c.103 - 105del CTG是在一名先天性肌营养不良的年轻患者尸检时发现的，该患者9岁时出现一度房室传导阻滞，随后发生几次室上性阵发性心动过速。两名患者首发症状为下肢肌肉无力，分别在26岁和38岁时出现心脏传导缺陷并需要植入起搏器。其中一名携带突变c.1339G>C的患者40岁时死于难治性心力衰竭；另一名携带突变265C>T的患者30岁时死于血栓栓塞事件。携带突变1579C>T的患者表现为无心脏受累的经典LGMD表型，68岁时死于呼吸功能不全。
