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Abstract：
BACKGROUND: Hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) are the most frequent cardiomyopathies that cause acute heart failure and sudden cardiac death. Previous genetic reports have shown that pathogenic variants of genes encoding Z-disc components such as telethonin protein (TCAP) are the primary cause of DCM and HCM.
METHODS: This study was the first investigation on the TCAP gene among the Iranian cardiomyopathies population wherein the TCAP gene was analyzed in 40 unrelated patients (17 females and 23 males) who were clinically diagnosed with HCM and DCM. In addition, we conducted a thorough review of all published articles and the databases that were the first to report novel pathogenic or likely pathogenic variants the in TCAP gene.
RESULTS: In the cohort of this study, we identified only one intronic variant c.111-42G > A in one of the HCM patients that were predicted as polymorphism by in-silico analysis. Moreover, a total of 44 variants were reported for the TCAP gene in the literature where a majority of mutations were found to be missense. Pathogenic mutations in TCAP may cause diseases including limb-girdle muscular dystrophy 2G (LGMD-2G), DCM, HCM, intestinal pseudo-obstruction, and telethonin deficiency. However, a large number of affected patients were clinically diagnosed with limb-girdle 2G compared to other presenting phenotypes.
CONCLUSIONS: These findings suggest that the TCAP gene pathogenic mutations might not be a common cause of cardiomyopathies among Iranian patients. These gene disease-causing mutations may cause various manifestations, but it has a high prevalence among LGMD-2G, HCM, and DCM patients.
METHODS: This study was the first investigation on the TCAP gene among the Iranian cardiomyopathies population wherein the TCAP gene was analyzed in 40 unrelated patients (17 females and 23 males) who were clinically diagnosed with HCM and DCM. In addition, we conducted a thorough review of all published articles and the databases that were the first to report novel pathogenic or likely pathogenic variants the in TCAP gene.
RESULTS: In the cohort of this study, we identified only one intronic variant c.111-42G > A in one of the HCM patients that were predicted as polymorphism by in-silico analysis. Moreover, a total of 44 variants were reported for the TCAP gene in the literature where a majority of mutations were found to be missense. Pathogenic mutations in TCAP may cause diseases including limb-girdle muscular dystrophy 2G (LGMD-2G), DCM, HCM, intestinal pseudo-obstruction, and telethonin deficiency. However, a large number of affected patients were clinically diagnosed with limb-girdle 2G compared to other presenting phenotypes.
CONCLUSIONS: These findings suggest that the TCAP gene pathogenic mutations might not be a common cause of cardiomyopathies among Iranian patients. These gene disease-causing mutations may cause various manifestations, but it has a high prevalence among LGMD-2G, HCM, and DCM patients.
摘要：
背景：肥厚型心肌病（HCM）和扩张型心肌病（DCM）是引起急性心力衰竭和心源性猝死的最常见的心肌病。先前的遗传报告表明，编码Z-disc成分的基因的致病变体，例如端花素蛋白（TCAP）是DCM和HCM的主要原因。
方法：这项研究是对伊朗心肌病人群中TCAP基因的首次调查，其中在临床诊断为HCM和DCM的40例无关患者（17例女性和23例男性）中分析了TCAP基因。此外,我们对所有发表的文章和最早报道TCAP基因中新型致病或可能致病变异的数据库进行了全面回顾.
结果：在本研究的队列中，我们在其中一名HCM患者中仅鉴定出一个内含子变异c.111-42G>A,通过计算机模拟分析预测为多态性.此外，文献中报道的TCAP基因共有44个变异体,其中发现大多数突变为错义.TCAP中的致病突变可能导致疾病，包括肢带型肌营养不良2G（LGMD-2G），DCM,HCM,肠道假性梗阻,和端花素缺乏症.然而,与其他表型相比,大量受影响的患者在临床上被诊断为肢带2G.
结论：这些研究结果表明，TCAP基因致病突变可能不是伊朗患者心肌病的常见原因。这些基因致病突变可引起各种表现,但它在LGMD-2G中的患病率很高，HCM,和DCM患者。
方法：这项研究是对伊朗心肌病人群中TCAP基因的首次调查，其中在临床诊断为HCM和DCM的40例无关患者（17例女性和23例男性）中分析了TCAP基因。此外,我们对所有发表的文章和最早报道TCAP基因中新型致病或可能致病变异的数据库进行了全面回顾.
结果：在本研究的队列中，我们在其中一名HCM患者中仅鉴定出一个内含子变异c.111-42G>A,通过计算机模拟分析预测为多态性.此外，文献中报道的TCAP基因共有44个变异体,其中发现大多数突变为错义.TCAP中的致病突变可能导致疾病，包括肢带型肌营养不良2G（LGMD-2G），DCM,HCM,肠道假性梗阻,和端花素缺乏症.然而,与其他表型相比,大量受影响的患者在临床上被诊断为肢带2G.
结论：这些研究结果表明，TCAP基因致病突变可能不是伊朗患者心肌病的常见原因。这些基因致病突变可引起各种表现,但它在LGMD-2G中的患病率很高，HCM,和DCM患者。
