NEW YORK – New research has revealed dozens of genes containing inherited or

纽约——新研究揭示了数十个包含遗传性或

de novo

从头开始

alterations that increase the risk of congenital heart disease, congenital heart malformations that can lead to infant mortality, or long-term complications affecting the heart and other systems.

增加先天性心脏病风险的变异、可能导致婴儿死亡的先天性心脏畸形，或影响心脏和其他系统的长期并发症。

As they reported in the

正如他们在报告中所述

Proceedings of the National Academy of Sciences

美国国家科学院院刊

on Monday, researchers from Yale School of Medicine, Rockefeller University, Washington University, and other centers used targeted molecular inversion probe (MIP) panel sequencing to search for damaging inherited or

周一，耶鲁医学院、洛克菲勒大学、华盛顿大学和其他中心的研究人员使用靶向分子反向探针（MIP）面板测序来寻找有害的遗传或

de novo

从头开始

mutations across 248 genes in 5,929 clinically phenotyped individuals with CHD from the Pediatric Cardiac Genomics Consortium effort. They also brought in exome sequencing profiles for another 3,887 parent-child trios and 1,739 singleton CHD cases from the Pediatric Heart Network.

来自儿科心脏基因组联盟项目的5,929名具有临床表型的先天性心脏病（CHD）患者的248个基因的突变数据。他们还整合了来自儿科心脏网络的另外3,887个父母-孩子三人组和1,739个单一CHD病例的外显子组测序数据。

Together, the sequence data highlighted 60 genes with higher-than-usual rates of

在一起，序列数据突显了60个基因，其变异率高于平常。

de novo

从头开始

mutations in 60 genes, including 13 genes not linked to CHD in the past. These

60个基因的突变，其中包括过去未与先天性心脏病相关的13个基因。这些

de novo

从头开始

and inherited variants, which were predicted to be damaging, turned up in just over 10 percent of the CHD cases considered.

预测为有害的遗传变异出现在刚刚超过10%的考虑中的CHD病例中。

'The clinical implications for prevention and mitigation provided by early molecular diagnosis are increasingly apparent and support the routine use of genomic analysis in evaluation of CHD,' co-senior and co-corresponding authors Richard Lifton, a human genetics and genomics researcher with Rockefeller University, and Martina Brueckner, a genetics and pediatrics researcher with Yale School of Medicine, and their colleagues wrote..

“早期分子诊断在预防和缓解方面的临床意义日益明显，这支持了在先天性心脏病评估中常规使用基因组分析，”资深作者兼通讯作者、洛克菲勒大学的人类遗传学与基因组学研究员理查德·利夫顿以及耶鲁医学院的遗传学和儿科学研究员玛蒂娜·布吕克纳及其同事写道。

When the team focused on phenotypes associated with the variants, it found single cardiac phenotype manifestations for alterations in 33 of the genes. Variants in the cardiac alpha-myosin heavy chain-coding gene and 11 other genes had more variable phenotypes, on the other hand, showing apparent ties to as many as four CHD subtypes.

当研究团队专注于与这些变异相关的表型时，发现33个基因的改变出现了单一的心脏表型表现。而编码心脏α-肌球蛋白重链的基因及其他11个基因的变异则表现出更多样的表型，与多达四种先天性心脏病亚型存在明显关联。

Another 15 genes contained damaging CHD-associated variants that did not coincide with any of the CHD subtypes or symptom clusters..

另有15个基因包含与CHD相关但不与任何CHD亚型或症状簇重合的有害变异。

Isolated CHD was linked to variants in seven genes, particularly genes with enhanced or selective expression in the cardiomyocyte lineage, the investigators reported. Meanwhile, they noted that at least 37 genes — including brain-expressed genes linked to neurodevelopmental delay — appeared to influence phenotypes or symptoms found beyond the heart..

研究人员报告说，孤立性先天性心脏病与七个基因的变异有关，特别是那些在心肌细胞谱系中表达增强或选择性表达的基因。同时，他们指出，至少有 37 个基因（包括与神经发育迟缓相关的大脑表达基因）似乎会影响心脏以外发现的表型或症状。

'Mutations often produced variable congenital heart disease (CHD) and extracardiac (EC) phenotypes,' the authors reported, noting that '[p]robands with mutations associated with syndromic CHD were frequently not clinically diagnosed, often due to the absence of characteristic phenotypes.'

“作者报告说：‘基因突变常常导致多种不同的先天性心脏病（CHD）和心脏外（EC）表型，’并指出‘与综合征型CHD相关的基因突变患者常常未被临床诊断，通常是由于缺乏典型的表型特征所致。’”

Together, the authors suggested the new findings 'demonstrate the significantly greater precision of molecular diagnosis of CHD to establish an early diagnosis for the syndromic genes frequently mutated in CHD.'

作者们共同指出，新发现“证明了分子诊断在先天性心脏病（CHD）中建立早期诊断的显著更高精确性，特别是针对在CHD中频繁突变的综合征相关基因。”