Laboratory for Molecular Medicine, Partners HealthCare Center for Personalized Genetic Medicine, Cambridge, Massachusetts 02139, USA.
Genet Med. 2010 May;12(5):268-78. doi: 10.1097/GIM.0b013e3181d6f7c0.
Genetic tests for the most commonly mutated genes in dilated cardiomyopathy (DCM) can confirm a clinical diagnosis in the proband and inform family management. Presymptomatic family members can be identified, allowing for targeted clinical monitoring to minimize adverse outcomes. However, the marked locus and allelic heterogeneity associated with DCM have made clinical genetic testing challenging. Novel sequencing platforms have now opened up avenues for more comprehensive diagnostic testing while simultaneously decreasing test cost and turn around time.
By using a custom design based on triplicate resequencing and separate genotyping of known disease-causing variants, we developed the DCM CardioChip for efficient analysis of 19 genes previously implicated in causing DCM.
The chip's analytical sensitivity for known and novel substitution variants is 100% and 98%, respectively. In screening 73 previously tested DCM patients who did not carry clinically significant variants in 10 genes, 7 variants of likely clinical significance were identified in the remaining 9 genes included on the chip. Compared with traditional Sanger-based sequencing, test cost and turn around time were reduced by approximately 50%.
The DCM CardioChip is a highly efficient screening test with a projected clinical sensitivity of 26-29%.
针对扩张型心肌病（DCM）中最常见突变基因的基因检测，可在先证者中确认临床诊断，并为家族管理提供信息。可识别出无症状的家族成员，从而进行有针对性的临床监测，最大程度地减少不良后果。然而，与 DCM 相关的明显基因座和等位基因异质性使得临床基因检测具有挑战性。新型测序平台现在为更全面的诊断测试开辟了道路，同时降低了测试成本和周转时间。
通过使用基于三重复测序和已知致病变异单独基因分型的定制设计，我们开发了 DCM CardioChip，用于有效分析先前与 DCM 相关的 19 个基因。
该芯片对已知和新型替换变体的分析灵敏度分别为 100%和 98%。在对 73 名先前经过测试且在 10 个基因中未携带临床显著变异的 DCM 患者进行筛查时，在芯片上包含的其余 9 个基因中发现了 7 个可能具有临床意义的变异。与传统的基于 Sanger 的测序相比，测试成本和周转时间减少了约 50%。
DCM CardioChip 是一种高效的筛选测试，预计临床灵敏度为 26-29%。
