胎儿后颅窝异常种类繁多且遗传机制不明，超声表现相近的患儿预后可截然不同，为优生咨询带来极大困难。课题组前期应用染色体微阵列芯片分析（CMA）技术，在超声提示后颅窝异常而核型正常的胎儿中检出拷贝数变异（CNVs），发现了一些遗传综合征，提示CNVs可能是后颅窝异常的重要遗传机制。那么，各类后颅窝异常与CNVs的相关性是否相同？这些CNVs基因型与胎儿后颅窝异常的超声表型有着何种关联？以上科学问题的研究，其先决条件是胎儿后颅窝异常的准确诊断及精确分类。由此，本课题拟在前期研究基础上，以三维超声量化胎儿后颅窝异常超声表型为突破口，建立标准化产前分类诊断体系，并联合CMA检测胎儿后颅窝异常可能存在的遗传物质改变，以寻找表型与基因型的规律，创新性的建立胎儿后颅窝异常“超声表型-基因型”数据库。本项目的进行对促进结构-基因相结合的诊断方式、后颅窝异常遗传学机制的深入研究、指导优生优育具有重要意义。

There is a wide variety of posterior cranial fossa abnormalities (PFAs) in fetus, and their genetic mechanisms are not clear now. Even the fetuses with PFAs show very similar ultrasonographic appearance, the prognosis could be radically different. This distinct characteristic brings serious difficulties in prenatal genetic counseling. In our preliminary research, some genomic copy-number variants (CNVs) and related genetic syndromes were detected in certain cases of PFAs using chromosome microarray analysis (CMA). These cases with PFAs were firstly detected by prenatal ultrasound, and their karyotypes were shown normal. It is suggested that CNVs might be one of the significant genetic mechanisms for PFAs. So, whether the relationship between CNVs and different types of PFAs are the same? What kind of connection exists between the CNVs genotype and ultrasound phenotype in fetus with PFAs? To solve the scientific problem above, the prerequisite is to make an accurate diagnose and precise classification for fetus with PFAs. Therefore, this study attempt to apply three-dimensional ultrasound to quantify PFAs ultrasound phenotype in fetus which is based on our previous study, and develop a standardized prenatal classification system. Then the CMA methods were employed to identify genetic material variants in fetus with PFAs, in order to further explore the relationship between the PFAs genotype and phenotype, and finally establish a fetal ‘ultrasonic phenotype – genotype’ database of PFAs innovatively. PFAs ultrasound manifestation related genetic material database. This study will promote the clinical application of the ‘structure-genomics’ diagnostic pattern and conducive to further genetics pathogeny study of PFAs, that is significant in guiding aristogenesis.