张庆华，郝胜菊，闫有圣，胡秀琴，冯暄，梁济慈，栾桦

(甘肃省妇幼保健院，1. 医学遗传中心；2. 妇产科，兰州　730050)



复发性自然流产患者的遗传学多因素分析研究

张庆华1*，郝胜菊1，闫有圣1，胡秀琴1，冯暄1，梁济慈1，栾桦2

(甘肃省妇幼保健院，1. 医学遗传中心；2. 妇产科，兰州730050)

目的探讨复发性自然流产(RSA)发生与多种遗传学因素的相关性。方法收集928对RSA患者夫妇进行染色体核型分析，其中染色体核型为Y染色体多态性的男性进行Y染色体微缺失的多重连接探针扩增(MLPA)检测；同时对染色体核型正常的RSA女性患者进行亚甲基四氢叶酸还原酶(MTHFRC677T)、凝血因子Ⅴ G1691A和凝血酶原Ⅱ G20210A等遗传性易栓症相关基因多态性的测序分析。结果(1)928对RSA夫妇中，染色体异常核型的检出率为3.34%(31/928)，以染色体结构异常中的平衡易位为主(检出率2.37%)；染色体多态性核型的检出率为8.62%(80/928)，其中以Y染色体多态性为主(61.25%)；(2)49例Y染色体多态性核型的男性中，Y染色体微缺失的异常检出率高达10.20%(5/49)，以AZFc基因的微缺失和微重复为主；(3)153例染色体核型正常的RSA女性患者中，遗传性易栓症相关基因MTHFRC677T的多态性与RSA有关，且在显性及隐性遗传模式下，以隐性遗传模式的风险更高。而凝血因子Ⅴ G1691A和凝血酶原Ⅱ G20210A位点均为GG纯合基因型。结论RSA发生与染色体异常核型及多态性密切相关，尤其是其与Y染色体多态性的相关性不容忽视；另外，RSA的发生与遗传性易栓症相关基因MTHFRC677T的多态性亦有关。

复发性自然流产；染色体核型；Y染色体微缺失；遗传性易栓症基因多态性

【Abstract】

Objective： To evaluate the association between recurrent spontaneous abortion (RSA) and multiple genetic factors.

Methods： Chromosome karyotype of 928 RSA couples were analyzed. Among them，Y chromosome microdeletions of 49 male patients with Y chromosome heteromorphisms were detected by multiplex ligation-dependent probe amplification method (MLPA). Polymorphisms of hereditary thrombophilia-related genes (MTHFRC677T，factorⅤ G1691A andprothrombinⅡ G20210A) were analyzed for 153 female RSA patients with normal chromosome karyotype by sequencing.

Results： Among the 928 RSA couples，chromosomal abnormalities were detected in 3.14% of the couples (31/928) with chromosome balanced translocation as the major type (detection rate 2.4%). Chromosome heteromorphisms were detected in 8.62% of the couples (80/928)，and most of them were Y chromosome polymorphism (61.2%). Meanwhile，the frequency of abnormalities with Y microdeletion reached to 10.2% (5/49) in the 49 male patients with Y chromosome heteromorphisms，andAZFc microdeletion and microrepetition were the most frequently observed alteration. In the 153 female RSA patients with normal karyotypes，the polymorphisms ofMTHFRC677T gene maybe associated with the recurrent spontaneous abortion，and T polymorphism was one of risk factors for recurrent spontaneous abortion under recessive heredity models especially. BothfactorⅤ G1691A andprothrombinⅡ G20210A of the hereditary thrombophilia gene were GG homozygous genotype.

Conclusions： RSA is closely associated with chromosomal abnormalities and heteromorphisms，especially Y chromosome heteromorphisms. In addition，the occurrence of RSA is associated with hereditary thrombophilia related geneMTHFRC677T polymorphism.

(JReprodMed2016，25(8)：711-718)

复发性自……