Lamin A and C are nuclear matrix proteins which are located on the nuclear surface of the inner nuclear membrane. Both proteins are encoded by the same gene (LMNA) mapped to the region 1q21.2– 1q21.3 with 12 exons. Alternative splicing within exon 10 generates two different mRNAs that code for lamin A and C. Skeletal and myocardial laminopathies caused by mutations in this gene were first reported in 1999 (for reviews, see Fatkin et al., Bonn et al., Shackleton et al., and Genschel and Schmidt). The clinical spectrum ranges from LMNArelated congenital muscle dystrophy to later onset Emery–Dreifuss dystrophy, limb girdle dystrophy, familial partial lipodystrophy, Hutchinson–Gilford progeria syndrome to dilated cardiomyopathy, with conduction system disease depending on the form and site of the mutation. Patients with a predominant cardiac phenotype are characterized by atrial arrhythmia, progressive atrioventricular conduction disease, and ventricular tachycardia, that often precede the development of systolic dysfunction. To date, several other rare inherited human diseases with overlapping phenotypes have been linked to LMNA mutations, suggesting a clinical continuum between these clinical entities. The cause of laminopathies—not only those with predominant cardiac involvement—are mutations along the entire LMNA gene, although the majority are missense mutations in the central rod domain. The pathophysiological mechanisms are poorly understood as LMNA mutations may have effects on nuclear fragility, alterations in cellular signalling, and gene expression, resulting in abnormal interaction between lamins and other nuclear proteins such as desmin, and abnormal processing of pre-lamin A.

中文翻译：

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扩张型心肌病患者的 Lamin A/C 突变

Lamin A 和 C 是核基质蛋白，位于内核膜的核表面。两种蛋白质都由相同的基因 (LMNA) 编码，该基因映射到具有 12 个外显子的 1q21.2– 1q21.3 区域。外显子 10 内的选择性剪接产生两种不同的 mRNA，编码 lamin A 和 C。1999 年首次报道了由该基因突变引起的骨骼和心肌椎板病（综述见 Fatkin 等人、Bonn 等人、Shackleton 等人） .，以及根舍尔和施密特）。临床范围从 LMNA 相关的先天性肌肉营养不良到迟发的 Emery-Dreifuss 营养不良、肢带营养不良、家族性部分脂肪营养不良、Hutchinson-Gilford 早衰综合征到扩张型心肌病，传导系统疾病取决于突变的形式和部位。具有主要心脏表型的患者的特征是房性心律失常、进行性房室传导疾病和室性心动过速，这些通常先于收缩功能障碍的发展。迄今为止，其他几种具有重叠表型的罕见遗传人类疾病与 LMNA 突变有关，表明这些临床实体之间存在临床连续性。椎板病的原因——不仅是那些以心脏受累为主的那些——是整个 LMNA 基因的突变，尽管大多数是中央杆结构域的错义突变。病理生理机制知之甚少，因为 LMNA 突变可能对核脆性、细胞信号的改变和基因表达有影响，