先天性膈疝（CDH）是一种严重的出生缺陷性疾病，主要表现为先天性膈肌发育不全导致的腹腔脏器嵌入胸腔，常伴随肺发育异常。CDH在新生儿中的发病率为1/2500-1/3000，约占所有出生缺陷的8%以及所有新生儿死亡率的1-2%。 动物实验以及人类CDH的研究表明遗传因素比如染色体结构变异在其发生过程中起重要作用。但大部分的病例患者尤其是散发病例的发病原因及其致病基因并不十分清楚。本课题我们将招募100例父母-患病儿三口之家的样本，用全基因组芯片技术对患病病例进行全基因组致病新生染色体结构异常的鉴定；同时用二代靶向测序技术对约100个CDH的候选基因进行新生单核苷酸，插入缺失变异的研究，最终鉴定CDH的致病基因。本课题将收集CDH的遗传信息，为阐明该病的发病原因提供理论基础；为建立产前或者植入前遗传诊断提供现实依据并有效减少或者避免该疾病的发生，达到更有效的优生优育目的。

Congenital diaphragmatic hernia (CDH) is a serious birth defect characterized by incomplete formation of the diaphragm, resulting in herniation of the abdominal viscera into the chest cavity. The incidence of CDH is approximately 1 in 2,500 -3,000 live births, accounting for 8% of all major birth anomalies and 1-2% of neonatal mortality. Although the aetiology of CDH remains poorly understood, studies from animal models and patients with CDH suggest that genetic factors play an important role in the development of CDH. Genetic factors including aneuploidies and copy number variants (CNVs) are important in the pathogenesis of many cases of CDH, but few single genes have been definitively implicated in human CDH. In this study, we will recruit 100 parent-child trios using microarray analysis to investigate the de novo chromosomal anomalies and CNVs in genomics and select a set of CDH related training genes to prioritize the genes in those segmental aneuploidies and identify the genes that may contribute to the aetiology of CDH. We will also use the next generation targeted resequencing analysis to sequence 100 CDH related and candidate genes to identify de novo deleterious single nucleotide variants and frameshift indels. The goals of our research are to provide better prognostic information and accurate information about risk of recurrence to parents and providers, and to provide genetic basis for prenatal diagnosis/ preimplantation genetic diagnosis, consequently decreasing or avoiding the occurrence of CDH in babies.