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Laminopathies
Nucleus ( IF 2.7 ) Pub Date : 2018-12-17 , DOI: 10.1080/19491034.2018.1515606
Giovanna Lattanzi 1, 2 , Lorenzo Maggi 3 , David Araujo-Vilar 4
Affiliation  

Laminopathies are tissue-specific or systemic disorders caused by mutations in LMNA gene encoding lamin A/C (primary laminopathies) or in genes encoding proteins with structural and/or functional relationship with lamin A/C (secondary laminopathies). Since 1994, when the first laminopathy, type 1 Emery-Dreifuss Muscular Dystrophy, was associated to the EMD gene [1] and much more since 1999, when LMNA mutations were linked to the type 2 form of the same muscular dystrophy [2], the interest in lamin and nuclear envelope role in disease has grown exponentially. Even more because, unexpectedly, more than ten different clinical entities including disorders of adipose tissue, cardiomyopathies, and accelerated ageing syndromes have been linked to LMNA mutations in the following years and at least the same number of diseases have been associated with mutations in other nuclear envelope genes. This has in turn pushed forward basic research in the field of lamin and nuclear envelope function, and international highly engaged and motivated teams around the world have provided exciting advances in the understanding of pathologies and their molecular basis. The International Meeting on Laminopathies held in Bologna, Italy, on April 2017, brought together leading researchers in the field and initiated stimulated discussions and new cues for future research that we are presenting in the articles of this special issue of Nucleus on Laminopathies. We are extremely grateful to Nucleus and the colleagues who contributed the articles, and to all leading scientists and young researchers, who participated in the International Meeting on Laminopathies and shared their knowledge and ideas. We are also grateful to patients and their associations, who contributed their experience at the meeting and added knowledge to our understanding of diseases. This issue has a clear interdisciplinary structure, as had the International Meeting on Laminopathies, not only because it includes papers with a prevailing clinical approach and others mostly referring to molecular and biological advances in the study of lamin-linked mechanisms, but also because all clinical phenotypes are taken into account and common symptoms (such as cardiomyopathy or lipodystrophy), are discussed across different laminopathies. Moreover, the outcome of a variety of different experimental approaches, from epigenetics to cell biology is reported in the articles addressing lamindependent pathogenetic pathways. Clinical studies reported in the Nucleus issue provide an updated review of current knowledge of disease symptoms and management and are also intended as a starting point to collect more data and design new ad hoc studies to identify clinically useful predictors to stratify risk in mutation carriers, including probands and their asymptomatic relatives. Heart dysfunction, a symptom shared by Emery-Dreifuss Muscular Dystrophy, other neuromuscular laminopathies, Dilated Cardiomyopathy with conduction disease, as well as Hutchinson-Gilford Progeria and cases of Familial Partial Lipodystrophy, is the topic of several articles presenting new tools for early diagnosis, pharmacological and instrumental treatments and known pathomechanisms (Boriani, Brugada, Peretto). Aspects related to the age at onset and treatment of early onset forms of cardiolaminopathies are also discussed (Brugada). The Emery-Dreifuss muscular dystrophy neuromuscular phenotype is extensively described in the clinical papers, always with attention to the pathogenic mechanisms (MadeyPilarzyck). An unexpected common feature of EmeryDreifuss patients, the increase of circulating TGFbeta 2, and its effect on muscle and tendon cells are reported in the research article made possible by a wide collaborative study of the Italian Network for Laminopathies with the contribution of French researchers of the Muchir and Bonne group (Bernasconi). Papers on type 2 Familial partial lipodystrophy (Araujo-Vilar, Gambineri, Vigouroux) describe the most recent diagnostic criteria and therapeutic approaches and report interdisciplinary studies derived in long-lasting collaborations between clinicians and basic researchers that allowed the discovery of major players in disease mechanisms: NUCLEUS 2018, VOL. 9, NO. 1, 543–544 https://doi.org/10.1080/19491034.2018.1515606

中文翻译:

椎板病

椎板病是由编码 lamin A/C 的 LMNA 基因突变(原发性椎板病)或编码与 lamin A/C 具有结构和/或功能关系的蛋白质的基因突变引起的组织特异性或全身性疾病(继发性椎板病)。自 1994 年第一例椎板病,即 1 型 Emery-Dreifuss 肌营养不良症与 EMD 基因相关 [1] 以来,自 1999 年以来,LMNA 突变与同一肌营养不良症的 2 型相关 [2],对核纤层蛋白和核膜在疾病中的作用的兴趣呈指数增长。更重要的是,出乎意料的是,超过十种不同的临床实体,包括脂肪组织疾病、心肌病、在接下来的几年里,加速衰老综合征与 LMNA 突变有关,至少有相同数量的疾病与其他核被膜基因的突变有关。这反过来又推动了核纤层蛋白和核包膜功能领域的基础研究,世界各地高度参与和积极进取的国际团队在病理学及其分子基础的理解方面取得了令人振奋的进展。2017 年 4 月在意大利博洛尼亚举行的国际椎板病会议汇集了该领域的领先研究人员,并发起了激发讨论和未来研究的新线索,我们将在本期《核关于椎板病》的特刊文章中介绍这些线索。我们非常感谢 Nucleus 和贡献文章的同事,以及所有参加椎板病国际会议并分享他们的知识和想法的领先科学家和年轻研究人员。我们也感谢患者及其协会,他们在会议上贡献了他们的经验,并为我们对疾病的理解增加了知识。这个问题有一个清晰的跨学科结构,就像国际椎板病会议一样,不仅因为它包括具有流行临床方法的论文和其他主要涉及 lamin 相关机制研究中的分子和生物学进展的论文,还因为所有临床表型被考虑在内,常见症状(如心肌病或脂肪代谢障碍)在不同的椎板病中​​进行了讨论。此外,各种不同实验方法的结果,从表观遗传学到细胞生物学的研究在处理 lamin 依赖的致病途径的文章中有所报道。Nucleus 一期报道的临床研究提供了对当前疾病症状和管理知识的最新评论,也旨在作为收集更多数据和设计新的临时研究的起点,以确定临床上有用的预测因子,以对突变携带者的风险进行分层,包括先证者及其无症状亲属。心脏功能障碍是 Emery-Dreifuss 肌营养不良症、其他神经肌肉筋膜病、扩张型心肌病伴传导疾病以及 Hutchinson-Gilford 早衰症和家族性部分性脂肪代谢障碍病例共有的症状,是几篇提供早期诊断新工具的文章的主题,药物和仪器治疗以及已知的病理机制(Boriani、Brugada、Peretto)。还讨论了与发病年龄和早发型心肌病的治疗相关的方面(Brugada)。Emery-Dreifuss 肌营养不良症神经肌肉表型在临床论文中得到了广泛的描述,并始终关注其致病机制 (MadeyPilarzyck)。EmeryDreifuss 患者的一个意想不到的共同特征,循环 TGFbeta 2 的增加及其对肌肉和肌腱细胞的影响在研究文章中报告穆奇尔和博纳小组(贝纳斯科尼)。关于 2 型家族性部分脂肪代谢障碍的论文(Araujo-Vilar、Gambineri、Vigouroux) 描述了最新的诊断标准和治疗方法,并报告了临床医生和基础研究人员之间长期合作的跨学科研究,这些研究允许发现疾病机制的主要参与者:NUCLEUS 2018,VOL。9,没有。1, 543–544 https://doi.org/10.1080/19491034.2018.1515606
更新日期:2018-12-17
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