Rare de novo copy number variants in patients with congenital pulmonary atresia.
Rare de novo copy number variants in patients with congenital pulmonary atresia.
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先天性肺闭锁患者中罕见的从头拷贝数变异
DOI：
10.1371/journal.pone.0096471
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Tan ZP
中科院分区：
文献类型：
--
作者：
Xie L;Chen JL;Zhang WZ;Wang SZ;Zhao TL;Huang C;Wang J;Yang JF;Yang YF;Tan ZP
背景使用基因组微阵列和下一代测序的持续研究表明，基因对心血管疾病的贡献在过去被显著忽视。本研究的目的是鉴定先天性肺动脉闭锁（PA）个体中罕见的拷贝数变异。方法和结果基于包含关键基因的罕见结构变异在PA患者心脏发育中起重要作用的假设，我们使用Illumina SNP阵列平台对82名PA患者-父母三人组和189名对照组进行了高分辨率全基因组拷贝数变异（CNV）微阵列。在17/82例患者（20.7%）中发现了CNV，其中8例（9.8%）被认为是潜在致病性的。5个新生CNV发生在两个已知的先天性心脏病（CHD）位点（16p13.1和22q11.2）。首次发现了两个可能影响叶酸和维生素B12代谢的新生CNV。在17p13.2的从头1-Mb缺失可能代表一种罕见的基因组疾病，涉及轻度智力残疾和相关的面部特征。结论PA的发病机制中有9.8%是罕见的CNVs，提示PA的病因具有异质性和多效性。结合之前动物模型的数据，我们的研究结果可能有助于确定CHD和叶酸介导的一碳代谢（FOCM）之间的联系。随着高分辨率SNP阵列数据的积累，这些以前未描述的罕见CNV可能有助于揭示CHD中的关键基因，并可能为CHD发病机制提供新的见解。
Background Ongoing studies using genomic microarrays and next-generation sequencing have demonstrated that the genetic contributions to cardiovascular diseases have been significantly ignored in the past. The aim of this study was to identify rare copy number variants in individuals with congenital pulmonary atresia (PA). Methods and Results Based on the hypothesis that rare structural variants encompassing key genes play an important role in heart development in PA patients, we performed high-resolution genome-wide microarrays for copy number variations (CNVs) in 82 PA patient-parent trios and 189 controls with an Illumina SNP array platform. CNVs were identified in 17/82 patients (20.7%), and eight of these CNVs (9.8%) are considered potentially pathogenic. Five de novo CNVs occurred at two known congenital heart disease (CHD) loci (16p13.1 and 22q11.2). Two de novo CNVs that may affect folate and vitamin B12 metabolism were identified for the first time. A de novo 1-Mb deletion at 17p13.2 may represent a rare genomic disorder that involves mild intellectual disability and associated facial features. Conclusions Rare CNVs contribute to the pathogenesis of PA (9.8%), suggesting that the causes of PA are heterogeneous and pleiotropic. Together with previous data from animal models, our results might help identify a link between CHD and folate-mediated one-carbon metabolism (FOCM). With the accumulation of high-resolution SNP array data, these previously undescribed rare CNVs may help reveal critical gene(s) in CHD and may provide novel insights about CHD pathogenesis.
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DOI：
10.1161/circgenetics.111.961797
发表时间：
2012-04-01
期刊：
Circulation. Cardiovascular genetics
影响因子：
--
作者：
Arrington CB;Bleyl SB;Matsunami N;Bonnell GD;Otterud BE;Nielsen DC;Stevens J;Levy S;Leppert MF;Bowles NE
通讯作者：
Bowles NE
影响因子：
46.9
作者：
通讯作者：
--
影响因子：
--
作者：
Lee MS;Bonner JR;Bernard DJ;Sanchez EL;Sause ET;Prentice RR;Burgess SM;Brody LC
通讯作者：
Brody LC
影响因子：
2.1
作者：
Locke, Adam E.;Dooley, Kenneth J.;Tinker, Stuart W.;Cheong, Soo Yeon;Feingold, Eleanor;Allen, Emily G.;Freeman, Sallie B.;Torfs, Claudine P.;Cua, Clifford L.;Epstein, Michael P.;Wu, Michael C.;Lin, Xihong;Capone, George;Sherman, Stephanie L.;Bean, Lora J. H.
通讯作者：
Bean, Lora J. H.
影响因子：
3.6
作者：
Refsum, H
通讯作者：
Refsum, H