Pasotti Michele, Repetto Alessandra, Pisani Angela, Arbustini Eloisa
Dipartimento di Cardiologia, IRCCS Policlinico San Matteo, Pavia.
Ital Heart J Suppl. 2004 Feb;5(2):98-111.
The nuclear lamina is a proteinaceous layer apposed to the inner nuclear membrane. It is composed of a family of polypeptides, the lamins, highly conserved in evolution. In mammals, 3 lamins, A, B and C have been described with molecular weights ranging from 60,000 to 78,000 Da. Lamins A and C have close sequence homology. Lamins can be classified with the intermediate filament polypeptides and consist of a central rod domain flanked by globular and carboxyl domains. Lamins are synthesized into the cytoplasm: lamins B and C are transported from the cytoplasm into the nucleus and their sequences are not cleaved but remain a permanent feature of the mature polypeptide. Vice versa, lamin A is not synthesized as a large precursor polypeptide. The lamin A/C gene (LMNA) is mapped to 1q21.2-q21.3. Lamins are expressed in a wide range of tissues, including adult heart and skeletal muscle. Naturally occurring mutations in LMNA have been shown to be responsible for distinct diseases called laminopathies, including dilated cardiomyopathy with or without conduction defect and with or without variable skeletal muscle involvement. In the cardiological setting, conduction defects associated with dilated cardiomyopathy are now a reliable marker for LMNA gene molecular screening.
核纤层是附着于内核膜的蛋白质层。它由一族在进化中高度保守的多肽（核纤层蛋白）组成。在哺乳动物中，已描述了3种核纤层蛋白，A、B和C，分子量范围为60,000至78,000道尔顿。核纤层蛋白A和C具有紧密的序列同源性。核纤层蛋白可归类于中间丝多肽，由两侧为球状结构域和羧基结构域的中央杆状结构域组成。核纤层蛋白在细胞质中合成：核纤层蛋白B和C从细胞质转运至细胞核，其序列不被切割，而是成熟多肽的永久特征。相反，核纤层蛋白A不是作为大的前体多肽合成的。核纤层蛋白A/C基因（LMNA）定位于1q21.2 - q21.3。核纤层蛋白在广泛的组织中表达，包括成人心脏和骨骼肌。已证明LMNA中的自然发生突变是导致称为核纤层蛋白病的不同疾病的原因，包括伴有或不伴有传导缺陷以及伴有或不伴有可变骨骼肌受累的扩张型心肌病。在心脏病学领域，与扩张型心肌病相关的传导缺陷现在是LMNA基因分子筛查的可靠标志物。
