 在2009年7月的Nature Genetics上，发表了一篇名为：De novo copy number variants identify new genes and loci in isolated sporadic tetralogy of Fallot的文章。该文作者来自哈佛大学遗传研究中心、布莱汉姆妇女医院等多个研究机构。研究者首先对114例法四患儿的基因序列进行了全面扫描，这些患儿的父母都没有先心病史。结果发现了11个非常少见的基因拷贝数变异（CNVs）。随后他们对398例法四患儿进行了进一步研究，发现染色体3p25.1、7p21.3 和 22q11.2.等部位都会出现基因拷贝数变异。摘要如下： Tetralogy of Fallot (TOF), the most common severe congenital heart malformation, occurs sporadically, without other anomaly, and from unknown cause in 70% of cases. Through a genome-wide survey of 114 subjects with TOF and their unaffected parents, we identified 11 de novo copy number variants (CNVs) that were absent or extremely rare (<0.1%) in 2,265 controls. We then examined a second, independent TOF cohort (n = 398) for additional CNVs at these loci. We identified CNVs at chromosome 1q21.1 in 1% (5/512, P = 0.0002, OR = 22.3) of nonsyndromic sporadic TOF cases. We also identified recurrent CNVs at 3p25.1, 7p21.3 and 22q11.2. CNVs in a single subject with TOF occurred at six loci, two that encode known (NOTCH1, JAG1) disease-associated genes. Our findings predict that at least 10% (4.5–15.5%, 95% confidence interval) of sporadic nonsyndromic TOF cases result from de novo CNVs and suggest that mutations within these loci might be etiologic in other cases of TOF. 此项研究为明确先天性心脏病的遗传基因学开创了一个重要的先例，随着SNP技术的快速进展，目前可以快速对基因进行全序列扫描（genotyping），进而可以更加全面的评估引起先天性心脏病的遗传学病因；于此同时，这也必将为准备养小孩的年轻父母的优生优育提供更加有力的遗传学评估。 |
