The role of sarcomere gene mutations in patients with idiopathic dilated cardiomyopathy
The role of sarcomere gene mutations in patients with idiopathic dilated cardiomyopathy
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DOI：
10.1038/ejhg.2009.34
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发表时间：
2009-10-01
影响因子：
5.2
通讯作者：
Kober, Lars
中科院分区：
文献类型：
--
作者：
Moller, Daniel Vega;Andersen, Paal Skytt;Kober, Lars
我们对31名患有特发性扩张型心肌病（IDC）的无亲缘关系的丹麦患者队列进行了研究，以评估肌节蛋白基因突变在IDC中所起的作用。通过毛细管电泳单链构象多态性对患者进行基因筛查，随后对MYH7、MYBPC3、TPM1、ACTC、MYL2、MYL3、TNNT2、CSRP3和TNNI3编码区的构象异构体进行双向DNA测序。8名先证者携带疾病相关的基因变异（26%）。在MYH7中发现了3种新突变；在MYBPC3中发现了1种新的变异和2种已知突变；在TNNT2中发现了1种已知突变。1名先证者为双重杂合子。我们发现了表型可塑性的证据：在4例IDC患者中发现了3种先前被描述为导致肥厚型心肌病（HCM）的突变，且无肥厚期病史。此外，1个家系出现了多例典型的扩张型心肌病以及1例左心室致密化不全。在约四分之一的IDC患者中发现了致病变异的肌节基因突变，并且似乎在疾病的病因中起重要作用。其遗传学情况与在肥厚型心肌病中所见的一样复杂。因此，我们的数据表明，即使没有疾病家族史，基因检测也应包括对最主要的肌节基因的筛查。《欧洲人类遗传学杂志》（2009年）17卷，1241 - 1249页；doi:10.1038/ejhg.2009.34；2009年3月18日在线发表
We investigated a Danish cohort of 31 unrelated patients with idiopathic dilated cardiomyopathy (IDC), to assess the role that mutations in sarcomere protein genes play in IDC. Patients were genetically screened by capillary electrophoresis single strand conformation polymorphism and subsequently by bidirectional DNA sequencing of conformers in the coding regions of MYH7, MYBPC3, TPM1, ACTC, MYL2, MYL3, TNNT2, CSRP3 and TNNI3. Eight probands carried disease-associated genetic variants (26%). In MYH7, three novel mutations were found; in MYBPC3, one novel variant and two known mutations were found; and in TNNT2, a known mutation was found. One proband was double heterozygous. We find evidence of phenotypic plasticity: three mutations described earlier as HCM causing were found in four cases of IDC, with no history of a hypertrophic phase. Furthermore, one pedigree presented with several cases of classic DCM as well as one case with left ventricular non-compaction. Disease-causing sarcomere gene mutations were found in about one-quarter of IDC patients, and seem to play an important role in the causation of the disease. The genetics is as complex as seen in HCM. Thus, our data suggest that a genetic work-up should include screening of the most prominent sarcomere genes even in the absence of a family history of the disease. European Journal of Human Genetics (2009) 17, 1241-1249; doi: 10.1038/ejhg.2009.34; published online 18 March 2009