FMR1基因CGG重复数在复发性流产人群中的分布及卵巢功能相关性研究

Distribution of CGG repeats of FMR1 gene in patients with recurrent abortion and its correlation with ovarian function

目的探索新疆乌鲁木齐复发性流产患者脆性X智力低下基因1基因(CGG)n重复次数的分布状态,以及与卵巢功能的相关性。方法收集2017年6月至2019年1月就诊于新疆乌鲁木齐市新疆医科大学第一附属医院妇科,生殖医学中心的复发性流产患者,均在28w前有连续2次或2次以上的妊娠终止。抽血提取基因组DNA、应用AmplideXTMFMR1PCR专利技术进行PCR扩增以及毛细管电泳技术对血液标本进行FMR1基因(CGG)n重复基因进行检测,并对数据进行统计分析。结果对新疆乌鲁木齐48名复发性流产患者进行了FMR1(CGG)n的检测,在所有检测样本中,共检测到13种等位基因,CGG重复序列范围为20-54,98%的样本两个等位FMR1基因的(CGG)n为野生型,2%为突变杂合型。其中29(33.3%)和30(25.1%)最常见,其次为32,31。在整个检测队列中,我们发现了1例灰色区域,CGG拷贝数为54,未发现前突变样本和全突变样本。FMRl(CGG)n重复序列和基因型别与抗苗勒氏激素进行组间比较,差异王(P>0.05)。结论FMRl(CGG)n重复序列和基因型别与卵巢功能无相关性。新疆乌鲁木齐复发性流产患者FMR1(CGG)n重复序列与基因型别分布,与既往国内研究相似,但变异范围存在升高趋势,且呈高度集中分布。FMR1基因灰色区域等位基因的发病率明显高于亚洲及国内发病率,预测FMR1基因的(CGG)n可能与复发性流产有关,但仍需大样本数据的进一步证实。

Objective:To explore the distribution of fragile X mental retardation gene 1(CGG)n repetition frequency and its correlation with ovarian function in patients with recurrent abortion in Urumqi,Xinjiang.Methods:From June 2017 to January 2019,patients with recurrent abortion who visited the Department of Gynecology and Reproductive Medicine Center of the First Affiliated Hospital of Xinjiang Medical University in Urumqi,Xinjiang,were all terminated twice or more in a row before 28 weeks.Genomic DNA was extracted from blood samples,and FMR1 gene(CGG)n duplicate gene was detected by Amplide XTM FMR1 PCR patented technology and capillary electrophoresis.The data were analyzed statistically.Results:FMR1(CGG)n was detected in 48 patients with recurrent abortion in Urumqi,Xinjiang.Thirteen alleles were detected in all samples.The repeat sequence of CGG ranged from 20 to 54.Two alleles of FMR1(CGG)n in 98%of the samples were wild type and 2%were mutant heterozygous.29(33.3%)and 30(25.1%)were the most common,followed by 32,31.In the whole detection queue,we found a grey region with 54 copies of CGG.No pre-mutation and full-mutation samples were found.The repeat sequence and genotype of FMRl(CGG)n were compared with those of anti-Mullerian hormone,and the difference was king(P>0.05).Conclusion:There is no correlation between FMRl(CGG)n repeat sequence and genotype and ovarian function.The distribution of FMR1(CGG)n repeats and genotypes in patients with recurrent abortion in Urumqi,Xinjiang,is similar to previous studies in China,but the variation range tends to increase and is highly concentrated.The incidence of gray region allele of FMR1 gene is significantly higher than that of Asia and China.It is predicted that CGG n of FMR1 gene may be related to recurrent abortion,but it still needs further confirmation from large sample data.