Obscurin variants and inherited cardiomyopathies.
Obscurin variants and inherited cardiomyopathies.
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DOI：
10.1007/s12551-017-0264-8
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发表时间：
2017-06
影响因子：
--
通讯作者：
Marston S
中科院分区：
文献类型：
--
作者：
Marston S
肥厚型心肌病（HCM）、扩张型心肌病（DCM）和左心室致密化不全（LVNC）等遗传性心肌病常与肌节蛋白突变相关。近年来，DNA测序技术的进步使得对肌节中巨大蛋白质的研究成为可能，如肌联蛋白和星云蛋白。尽管2007年有一份关于HCM相关的obscurin突变的孤立报告，但在这些研究中，obscurin在某种程度上被忽视了，这主要是因为它的功能作用远未明确。最近，全外显子组测序方法（WES）已被用于解决OBSCN（obscurin的基因）中的突变，发现OBSCN变体在遗传性心肌病中相对常见。在不同的研究中，在30例终末期衰竭心脏中发现了5种OBSCN独特变异，在74例HCM病例中发现了6种OBSCN独特变异，在10例LVNC患者中发现了3种OBSCN独特变异。到目前为止，已知的潜在致病OBSCN变体的数量相当少。其原因是OBSCN基因的突变直到最近才被认为是潜在的致病因素，并且没有被纳入大规模遗传调查中。OBSCN突变可能是HCM，DCM和LVNC和其他心肌病的原因，或者它们可能与相同或其他基因中的其他变体协同工作以启动病理。目前，obscurin的功能还不清楚，但我们预计，当测试大量可用的患者序列时，将发现更多与心肌病相关的OBSCN变体。我们希望，obscurin在病理学中的重要性的建立将刺激obscurin功能的彻底调查。
The inherited cardiomyopathies, hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM) and left ventricular non-compaction (LVNC), have been frequently associated with mutations in sarcomeric proteins. In recent years, advances in DNA sequencing technology has allowed the study of the giant proteins of the sarcomere, such as titin and nebulin. Obscurin has been somewhat neglected in these studies, largely because its functional role is far from clear, although there was an isolated report in 2007 of obscurin mutations associated with HCM. Recently, whole exome sequencing methodology (WES) has been used to address mutations in OBSCN, the gene for obscurin, and OBSCN variants were found to be relatively common in inherited cardiomyopathies. In different studies, 5 OBSCN unique variants have been found in a group of 30 end-stage failing hearts, 6 OBSCN unique variants in 74 HCM cases and 3 OBSCN unique variants in 10 LVNC patients. As yet, the number of known potentially disease-causing OBSCN variants is quite small. The reason for this is that mutations in the OBSCN gene have not been recognised as potentially disease-causing until recently, and were not included in large-scale genetic surveys. OBSCN mutations may be causative of HCM, DCM and LVNC and other cardiomyopathies, or they may work in concert with other variants in the same or other genes to initiate the pathology. Currently, the function of obscurin is not well understood, but we anticipate that many more OBSCN variants linked to cardiomyopathy will be found when the large cohorts of patient sequences available are tested. It is to be hoped that the establishment of the importance of obscurin in pathology will stimulate a thorough investigation of obscurin function.