Bonne Gisèle, Quijano-Roy Susana
Inserm, U974; Université Pierre et Marie Curie - Paris 6, UM 76; CNRS, UMR 7215; Institut de Myologie, and AP-HP - U.F. Cardiogénétique et Myogénétique, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
Handb Clin Neurol. 2013;113:1367-76. doi: 10.1016/B978-0-444-59565-2.00007-1.
The nuclear envelopathies, more frequently known as laminopathies are a rapidly expanding group of human hereditary diseases caused by mutations of genes that encode proteins of the nuclear envelope. The most frequent and best known form is Emery-Dreifuss muscular dystrophy (EDMD), a skeletal myopathy characterized by progressive muscular weakness, joint contractures, and cardiac disease. EMD gene, encoding emerin, causes the X-linked form of EDMD, while LMNA gene encoding lamins A and C, is responsible for autosomal forms, usually with a dominant transmission. In the last years, the spectrum of conditions has been extraordinarily enlarged, from a congenital muscular dystrophy with severe paralytic or rapidly progressive picture due to de novo mutations in LMNA (L-CMD) to a limb-girdle muscular dystrophy with adult onset and much milder weakness (LGMD1B). LMNA has also been involved in a form of isolated cardiomyopathy associated with cardiac conduction disease and in an axonal form of hereditary neuropathy. Identification of this gene has been reported also in a number of non-neuromuscular disorders including lipodystrophy syndromes and a wide spectrum of premature aging syndromes ranging from mandibuloacral dysplasia to restrictive dermopathy. Mutations in other genes implicated in the processing or maturation of nuclear lamins have also been found. The extraordinary complexity of the molecular and pathophysiological mechanisms of these diseases is still not well known and the occurrence of modifying factors or genes is highly suspected. Identification of new genes and investigation of new therapeutic approaches are in progress.
核被膜病，通常更名为核纤层蛋白病，是由编码核被膜蛋白的基因突变引起的一类迅速增多的人类遗传性疾病。最常见且最知名的形式是埃默里 - 德赖富斯肌营养不良症（EDMD），这是一种骨骼肌病，其特征为进行性肌肉无力、关节挛缩和心脏病。编码emerin的EMD基因导致X连锁型EDMD，而编码核纤层蛋白A和C的LMNA基因则导致常染色体形式的EDMD，通常为显性遗传。在过去几年中，疾病谱已大幅扩大，从因LMNA基因新发突变导致的具有严重麻痹或快速进展症状的先天性肌营养不良症（L - CMD）到成人发病且症状轻得多的肢带型肌营养不良症（LGMD1B）。LMNA基因还与一种伴有心脏传导疾病的孤立性心肌病形式以及一种轴索性遗传性神经病有关。在包括脂肪营养不良综合征以及从下颌 - 肢端发育不良到限制性皮肤病等广泛的早衰综合征在内的许多非神经肌肉疾病中也报道了该基因的鉴定。在其他与核纤层蛋白加工或成熟相关的基因中也发现了突变。这些疾病的分子和病理生理机制异常复杂，目前仍不清楚，而且高度怀疑存在修饰因子或基因。新基因的鉴定和新治疗方法的研究正在进行中。
