Rapid molecular genetic diagnosis of hypertrophic cardiomyopathy by semiconductor sequencing.
Rapid molecular genetic diagnosis of hypertrophic cardiomyopathy by semiconductor sequencing.
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半导体测序快速诊断肥厚型心肌病
DOI：
10.1186/1479-5876-12-173
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发表时间：
2014-06-17
影响因子：
7.4
通讯作者：
Wang DW
中科院分区：
文献类型：
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作者：
Li Z;Huang J;Zhao J;Chen C;Wang H;Ding H;Wang DW;Wang DW
快速确定肥厚性心肌病（HCM）的复杂遗传基础对于更好地理解和优化管理这种常见的多基因心血管疾病至关重要。方法建立一种快速定制离子扩增子重测序方法，覆盖HCM的30个常见影响基因，并在120例无关HCM患者中进行验证，以促进该病的遗传诊断。有了这个hcm特异性的小组和仅20毫微克的输入基因组DNA，医生们第一次可以在一天内从血液样本中找到变异。结果该方法在30个HCM基因的CDS区平均获得595628个定位reads， 95.51%的目标reads (64.06 kb)， 490倍的碱基覆盖深度和93.24%的碱基覆盖均匀性。经过验证，我们在87%（120个样本中的104个）样本中检测到潜在的致病变异。通过Sanger测序对8份样本中随机选择的7个HCM基因进行检测，该HCM面板的敏感性为100%，假阳性率为5%。结论离子扩增子HCM重测序法是目前最快速、全面、经济、可靠的HCM基因诊断方法。
BackgroundRapidly determining the complex genetic basis of Hypertrophic cardiomyopathy (HCM) is vital to better understanding and optimally managing this common polygenetic cardiovascular disease.MethodsA rapid custom Ion-amplicon-resequencing assay, covering 30 commonly affected genes of HCM, was developed and validated in 120 unrelated patients with HCM to facilitate genetic diagnosis of this disease. With this HCM-specific panel and only 20 ng of input genomic DNA, physicians can, for the first time, go from blood samples to variants within a single day.ResultsOn average, this approach gained 595628 mapped reads per sample, 95.51% reads on target (64.06 kb), 490-fold base coverage depth and 93.24% uniformity of base coverage in CDS regions of the 30 HCM genes. After validation, we detected underlying pathogenic variants in 87% (104 of 120) samples. Tested seven randomly selected HCM genes in eight samples by Sanger sequencing, the sensitivity and false-positive-rate of this HCM panel was 100% and 5%, respectively.ConclusionsThis Ion amplicon HCM resequencing assay provides a currently most rapid, comprehensive, cost-effective and reliable measure for genetic diagnosis of HCM in routinely obtained samples.
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影响因子：
46.9
作者：
Loman, Nicholas J.;Misra, Raju V.;Pallen, Mark J.
通讯作者：
Pallen, Mark J.
影响因子：
9.1
作者：
Ho, Carolyn Y.
通讯作者：
Ho, Carolyn Y.
影响因子：
37.8
作者：
Ho CY
通讯作者：
Ho CY
影响因子：
--
作者：
Meder, Benjamin;Haas, Jan;Rottbauer, Wolfgang
通讯作者：
Rottbauer, Wolfgang
影响因子：
30.8
作者：
Carvill, Gemma L.;Heavin, Sinead B.;Yendle, Simone C.;McMahon, Jacinta M.;O'Roak, Brian J.;Cook, Joseph;Khan, Adiba;Dorschner, Michael O.;Weaver, Molly;Calvert, Sophie;Malone, Stephen;Wallace, Geoffrey;Stanley, Thorsten;Bye, Ann M. E.;Bleasel, Andrew;Howell, Katherine B.;Kivity, Sara;Mackay, Mark T.;Rodriguez-Casero, Victoria;Webster, Richard;Korczyn, Amos;Afawi, Zaid;Zelnick, Nathanel;Lerman-Sagie, Tally;Lev, Dorit;Moller, Rikke S.;Gill, Deepak;Andrade, Danielle M.;Freeman, Jeremy L.;Sadleir, Lynette G.;Shendure, Jay;Berkovic, Samuel F.;Scheffer, Ingrid E.;Mefford, Heather C.
通讯作者：
Mefford, Heather C.