不明原因复发性流产女性FMR1基因CGG重复序列多态性研究

Polymorphism of CGG repeat sequence of FMR1 gene in women with unexplained recurrent spontaneous abortion

目的探讨不明原因复发性流产女性脆性X智力障碍1(FMRl)基因CGG重复序列多态性分布特点。方法收集2018年1月1日至2019年12月31日在石家庄市第四医院复发性流产门诊就诊的具有不明原因复发性流产史的340例患者为研究组;同期在石家庄市第四医院妇科门诊就诊的340例年龄匹配的无流产史女性为对照组。抽取外周血,提取基因组DNA,应用荧光PCR-毛细管电泳法进行FMR1基因CGG重复序列数检测,比较两组的CGG重复序列情况并加以分析。结果两组均无全突变型携带者。研究组中CGG重复序列数最多者为29次(41.5%),其后依次是30次(38.8%)和36次(8.2%);对照组CGG重复序列数最多者为29次(43.2%),其后依次为30次(42.6%)和31次(2.9%)。研究组和对照组FMRl基因CGG重复序列数均数比较无显著性差异[(29.29±5.31)vs.(28.88±5.97)](P>0.05)。研究组FMRl基因中间型携带率显著高于对照组(2.35%vs.0.29%)(P<0.05),CGG重复≥35次的正常等位基因携带率显著高于对照组(10.29%vs.3.53%)(P<0.05)。结论FMRl基因CGG重复序列等位基因中间型以及较大的正常型与不明原因复发性流产可能存在相关性。

Objective:To explore the distribution characteristics of polymorphism of CGG repeat sequence in fragile X mental retardation 1(FMR1)gene in women with unexplained recurrent spontaneous abortion(RSA).Methods:A total of 340 patients with unexplained RSA were collected as research group in the recurrent abortion clinic of the Fourth Hospital of Shijiazhuang from Jan 1,2018 to Dec 31,2019,while 340 age-matched women without abortion history were collected as the control group in the gynecological clinic.Genomic DNA was extracted from peripheral blood.The number of CGG repeats of FMR1 gene was detected by fluorescence PCR capillary electrophoresis and the CGG repeat sequences were compared and analyzed between the two groups.Results:The full mutation of FMR1 gene was not detected in all samples.The maximum frequency of CGG repeats was 29(41.5%),followed by 30(38.8%)and 36(8.2%)in the research group.The maximum frequency of CGG repeats was 29(43.2%),followed by 30(42.6%)and 31(2.9%)in the control group.The average number of CGG repeats was not significantly different between two groups[(29.29±5.31)vs.(28.88±5.97),P>0.05].The frequency of carriers with intermediate alleles in research group was significantly higher than that in the control group(2.35%vs.0.29%,P<0.05).The frequency of normal alleles with≥35 CGG repeats in research group was also significantly higher than the control group(10.29%vs.3.53%,P<0.05).Conclusions:There may be correlation between CGG repeat allele intermediate type and larger normal type of FMR1 gene and unexplained recurrent spontaneous abortion.