80例中国汉人复发性葡萄胎的临床特征及相关基因的致病性研究

发布时间：2018-06-22 03:30

本文选题：复发性葡萄胎 + 年龄　；参考：《浙江大学》2017年硕士论文

【摘要】：背景:复发性葡萄胎指至少有过两次葡萄胎妊娠史,现在已经明确的相关致病基因有NLRP7和KHDC3L。该病患者通常难以正常妊娠,常有流产、死产、葡萄胎以及妊娠滋养细胞肿瘤病史。且有过一次葡萄胎的患者比普通人群更容易再次发生葡萄胎,初次葡萄胎后再发葡萄胎的概率大约在0.7%到2.6%之间。对于葡萄胎患者来说,15岁和45岁是两个高风险年龄组,尤其是有多次不良妊娠史的复发性葡萄胎患者中高龄产妇比例大大增加。因葡萄胎恶变需接受化疗的患者大约在10%-25%之间。除了因化疗带来的副作用外,困扰复发性葡萄胎患者另一主要问题就是不育,当有葡萄胎致病基因NLRP7和KHDC3L基因存在突变时正常妊娠更加困难。目的:通过回顾性分析复发性葡萄胎患者的临床资料,统计其年龄、生育结局、恶变情况等数据,分析相关基因NLRP7和KHDC3L,探讨复发性葡萄胎的临床特征及NLRP7和KHDC3L的致病性。方法:回顾性分析80例2003年至2016年在浙江大学医学院附属第一医院及浙江大学医学院附属妇产科医院门诊就诊的中国汉人复发性葡萄胎患者,统计其初次患葡萄胎的年龄、再次发生葡萄胎的年龄、各次葡萄胎发生的时间间隔、葡萄胎组织病理类型、葡萄胎恶变率及生育史等临床资料并进行随访,且对所有患者进行NLRP7以及KHDC3L基因分析。结果:1.复发性葡萄胎患者的初发年龄集中在26-30岁之间,各次葡萄胎发生的时间间隔大部分是在13-24个月,其组织病理类型主要是完全性葡萄胎。80例复发性葡萄胎患者中只有17例患者有正常生育结局,其中有3例患者通过卵胞浆内单精子显微注射成功妊娠。80例复发性葡萄胎患者共有188次葡萄胎史,其中有24次葡萄胎妊娠恶变为妊娠滋养细胞肿瘤,总恶变率为12.77%。2.通过对NLRP7和KHDC3L的分析,我们在其中21例患者的NLRP7基因上证实了 19个突变位点,其中16例患者有NLRP7基因双位点突变,5例患者只有NLRP7基因单位点突变。在所有患者中并未发现KHDC3L基因突变。无论是单位点突变还是双位点突变,突变位点所在功能区主要是集中在LRR区域。结论:复发性葡萄胎患者的初发年龄与单次葡萄胎患者的发病年龄之间并无差异,在病理组织类型上完全性葡萄胎比部分性葡萄胎更具有侵袭性,更易恶变为妊娠滋养细胞肿瘤。除了恶变外,复发性葡萄胎对患者最大的影响就是不良妊娠结局,尤其是存在NLRP7基因突变的个体。虽然辅助生殖技术可以使复发性葡萄胎患者成功妊娠,但并不能解决所有患者的不育问题。
[Abstract]:Background: recurrent hydatidiform mole refers to at least two history of gestation of hydatidiform mole. NLRP7 and KHDC3L have been identified as the related pathogenic genes. Patients with the disease often have difficult pregnancies, including miscarriages, stillbirths, hydatidiform mole, and gestational trophoblastic neoplasms. Patients with one mole were more likely to reoccur than the general population, and the probability of reoccurrence was between 0.7% and 2.6% after the first mole. For hydatidiform mole patients, 15 and 45 years of age are two high-risk age groups, especially in recurrent hydatidiform mole patients with multiple adverse pregnancies. About 10-25% of patients with hydatidiform mole cancer need chemotherapy. In addition to the side effects caused by chemotherapy, another major problem for recurrent hydatidiform mole patients is infertility. It is more difficult for normal pregnancy to have mutations in the pathogenic genes NLRP7 and KHDC3L of hydatidiform mole. Objective: to study the clinical features of recurrent hydatidiform mole and the pathogenicity of NLRP7 and KHDC3L. Methods: 80 cases of recurrent hydatidiform mole from 2003 to 2016 in the first affiliated Hospital of Zhejiang University Medical College and the affiliated Obstetrics and Gynecology Hospital of Zhejiang University Medical College were retrospectively analyzed. The age, time interval, histopathological type, malignant rate and fertility history of hydatidiform mole were followed up. NLRP7 and KHDC3L gene were analyzed in all the patients. The result is 1: 1. The initial age of recurrent hydatidiform mole patients is mainly between 26 and 30 years old, and the intervals between the occurrence of each mole are mostly 13-24 months. The histopathological types were mainly complete hydatidiform mole. Only 17 of 80 recurrent hydatidiform mole patients had normal reproductive outcomes. Among them, 3 cases were successfully pregnant by intracytoplasmic sperm microinjection. 80 cases of recurrent hydatidiform mole had 188 history of hydatidiform mole. 24 cases of malignant transformation of hydatidiform mole into gestational trophoblastic tumor, the total malignant rate was 12.77. 2. Through the analysis of NLRP7 and KHDC3L, we confirmed 19 mutation sites of NLRP7 gene in 21 patients, of which 16 patients had NLRP7 double locus mutation and 5 patients had only NLRP7 unit mutation. No mutation of KHDC3L gene was found in all patients. Whether unit point mutation or double locus mutation, the functional region of mutation locus is mainly concentrated in LRR region. Conclusion: there is no difference between the initial age of recurrent hydatidiform mole and the onset age of single hydatidiform mole. Complete hydatidiform mole is more invasive than partial hydatidiform mole in pathological type. It is more likely to become gestational trophoblastic tumor. In addition to malignant change, recurrent hydatidiform mole has the greatest effect on the adverse pregnancy outcome, especially in individuals with NLRP7 gene mutation. Although assisted reproductive technology can lead to successful pregnancy in patients with recurrent hydatidiform mole, it does not solve the problem of infertility in all patients.
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R737.33

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