King's College London, Randall Division of Cell and Molecular Biophysics, New Hunt's House, Guy's Campus, London SE1 1UL, UK.
Biochem Soc Trans. 2010 Feb;38(Pt 1):257-62. doi: 10.1042/BST0380257.
A-type laminopathies are a group of diseases resulting from mutations in the intermediate filament proteins lamin A and C (both encoded by the LMNA gene), but for which the pathogenic mechanisms are little understood. In some laminopathies, there is a good correlation between the presence of a specific LMNA mutation and the disease diagnosed. In others however, many different mutations can give rise to the same clinical condition, even though the mutations may be distributed throughout one, or more, of the three functionally distinct protein domains of lamin A/C. Conversely, certain mutations can cause multiple laminopathies, with related patients carrying an identical mutation even having separate diseases, often affecting different tissues. Therefore clarifying genotype-phenotype links may provide important insights into both disease penetrance and mechanism. In the present paper, we review recent developments in genotype-phenotype correlations in laminopathies and discuss the factors that could influence pathology.
A 型层板病是一组由中间丝蛋白 lamin A 和 C（均由 LMNA 基因编码）突变引起的疾病，但对其发病机制知之甚少。在某些层板病中，特定的 LMNA 突变的存在与诊断出的疾病之间存在很好的相关性。然而，在其他情况下，许多不同的突变可以导致相同的临床情况，尽管突变可能分布在 lamin A/C 的一个或多个功能上不同的蛋白结构域中。相反，某些突变可导致多种层板病，具有相同突变的相关患者甚至患有不同的疾病，通常影响不同的组织。因此，阐明基因型-表型的联系可能为疾病的外显率和机制提供重要的见解。本文综述了层板病基因型-表型相关性的最新进展，并讨论了可能影响病理学的因素。
