Puckelwartz Megan, McNally Elizabeth M
University of Chicago, Chicago, IL 60637, USA.
Handb Clin Neurol. 2011;101:155-66. doi: 10.1016/B978-0-08-045031-5.00012-8.
Emery-Dreifuss muscular dystrophy (EDMD) is a progressive muscle-wasting disorder defined by early contractures of the Achilles tendon, spine, and elbows. EDMD is also distinctive for its association with defects of the cardiac conduction system that can result in sudden death. It can be inherited in an X-linked, autosomal dominant, or autosomal recessive fashion and is caused by mutations in proteins of the nuclear membrane. Mutations in the EMD gene, which encodes emerin, a transmembrane protein found at the inner nuclear membrane, are responsible for X-linked EDMD. The most common etiology of autosomal dominant EDMD is an LMNA gene mutation; LMNA encodes the intermediate filament protein lamins A and C, which constitute the major scaffolding protein of the inner nuclear membrane. Murine models of LMNA gene mutations have helped to identify different mechanisms of disease. Loss of LMNA function leads to nuclear fragility as well as other defects, such as abnormal nuclear function. Additional genes encoding nuclear membrane proteins such as SYNE1 and SYNE2 have also been implicated in EDMD, and in some cases their importance for cardiac and muscle function has been supported by animal modeling.
埃默里-德赖富斯肌营养不良症（EDMD）是一种进行性肌肉萎缩疾病，其特征为跟腱、脊柱和肘部早期挛缩。EDMD的另一个显著特点是与心脏传导系统缺陷有关，可导致猝死。它可以通过X连锁、常染色体显性或常染色体隐性方式遗传，由核膜蛋白的突变引起。编码emerin（一种在内核膜发现的跨膜蛋白）的EMD基因突变是X连锁EDMD的病因。常染色体显性EDMD最常见的病因是LMNA基因突变；LMNA编码中间丝蛋白核纤层蛋白A和C，它们构成内核膜的主要支架蛋白。LMNA基因突变的小鼠模型有助于识别不同的疾病机制。LMNA功能丧失会导致核脆弱以及其他缺陷，如异常的核功能。其他编码核膜蛋白的基因，如SYNE1和SYNE2，也与EDMD有关，在某些情况下，动物模型支持了它们对心脏和肌肉功能的重要性。
