Genetic cardiomyopathies (CM) are disorders that affect morphology and function of cardiac muscle. Significant number of genes have been implicated in causing the phenotype. It is one of the leading genetic causes of death in young. We performed a study to understand the genetic variants in primary cardiomyopathies in an Indian cohort. Study comprised of 22 probands (13 with family history) representing hypertrophic (n = 10), dilated (n = 7), restrictive (n = 2) and arrhythmogenic ventricular(n = 3) cardiomyopathies. Genomic DNA was target captured with a panel of 46 genes and libraries sequenced on Illumina platform. Analysis identified, reported pathogenic as well as novel pathogenic (n = 6) variants in 16 probands. Of the 10 HCM patients, candidate variants were identified in nine of them involving sarcomere genes (62%, MYBPC3, MYH6, MYH7, MYL3, TTN), Z-disc (10%, ACTN2, LDB3, NEXN,), desmosome (10%, DSG2, DSP, PKP2) cytoskeletal (4%, DTNA) and ion channel (10% RYR2). In four DCM patients, variants were identified in genes NEXN, LMNA and TTN. Three arrhythmogenic right ventricular cardiomyopathy (ARVD) patients carried mutations in desmosome genes. Rare TTN variants were identified in multiple patients. Targeted capture and sequencing resulted in identification of candidate variants in about 70% of the samples which will help in management of disease in affected individual as well as in screening and early diagnosis in asymptomatic family members. Amongst the analysed cases, 22% were inconclusive without any significant variant identified. Study illustrates the utility of next-generation multi-gene panel as a cost-effective genetic testing to screen all forms of primary cardiomyopathies.

遗传性心肌病（CM）是影响心肌形态和功能的疾病。大量基因与引起表型有关。它是年轻人死亡的主要遗传原因之一。我们进行了一项研究，以了解印度队列中原发性心肌病的遗传变异。研究由 22 名先证者（13 名有家族史）组成，他们分别患有肥厚型心肌病（n  = 10）、扩张型心肌病（n  = 7）、限制性心肌病（n  = 2）和致心律失常性室性心肌病（n  = 3）。基因组 DNA 是通过在 Illumina 平台上测序的一组 46 个基因和文库捕获的目标。分析确定并报告了 16 名先证者的致病性以及新的致病性 ( n  = 6) 变异。在 10 名 HCM 患者中，在其中 9 名患者中鉴定出候选变异，涉及肌节基因（62% ， MYBPC3、MYH6、MYH7、MYL3、TTN）、Z 盘（10%，ACTN2、LDB3、NEXN）、桥粒（10 %，DSG2，DSP，PKP2）细胞骨架（4%，DTNA）和离子通道（10% RYR2）。在四名 DCM 患者中，在基因 NEXN、LMNA 和 TTN 中发现了变异。三名致心律失常性右心室心肌病（ARVD）患者携带桥粒基因突变。在多名患者中发现了罕见的 TTN 变异。靶向捕获和测序在约 70% 的样本中鉴定出了候选变异，这将有助于控制受影响个体的疾病以及无症状家庭成员的筛查和早期诊断。在分析的病例中，22% 的病例未得出结论，未发现任何显着变异。研究说明了下一代多基因面板作为一种具有成本效益的基因测试来筛查所有形式的原发性心肌病的效用。