卵巢早衰定义为女性在40岁前发生卵巢功能衰竭，严重影响了患者的生活质量及生殖健康。卵巢早衰的病因复杂，目前尚不明确，极有可能与遗传基因有关。本课题组前期已收集一组珍贵的遗传性卵巢早衰家系患者的临床资料与血样，以此为突破口，研究卵巢早衰的遗传学机制。通过全基因连锁分析技术，微卫星遗传分子标记筛查基因，全基因组外显子捕获及深度测序技术鉴定突变位点，目前已初步筛选出某些基因突变位点与该遗传性卵巢早衰密切相关。以这些初筛突变位点为基础，继续深化利用以上技术，进一步明确与卵巢早衰相关基因突变。并在家系其他成员及特发性卵巢早衰患者中验证该突变。通过体外细胞定点突变、相关蛋白活性检测及在体靶向突变动物模型实验，进行突变基因功能验证，从而阐明卵巢早衰的分子遗传机制。本原创性研究有助解析卵巢早衰的发病机理，为早期干预卵巢早衰和遗传阻断提供理论基础，促进生殖健康，提高女性生活质量，兼具重大科研价值和社会意义。

Premature Ovarian Failure (POF) is defined as ovarian dysfunction occurs before age of forty, which jeopardizes women's life quality and reproductive health. The mechanism of POF involves a lot of unjustified theories, and gene mutation is one of the most possible theories. Our research group has done some work on collecting clinical materials and blood sample from a quite rare inheritable POF family and screening for potential mutation responsible for mechanism of POF by whole genome linkage analysis, micro-satellite genetic molecular marker screening, whole exome trapping and second generation sequencing. The primary results revealed that some genetic mutations have a strong correlation with the onset of POF. The next work is to testify the correlation with POF and function of genetic mutations. We intend to testify if these genetic mutations exist on other member of the POF family or other idiopathetic POF patients from the clinic. We also plan to check the function of genetic mutations by constructing cells with mutations of specific target gene, testing the activity of downstream protein of target mutant gene and building target-gene mutant animal model. With all work above accomplished, we will be able to clarify the genetic molecular mechanism of POF and preventing the early failure of ovary in order to improve women's life quality.