核苷酸微阵列技术在复发性流产发病机制及潜在致病位点中的应用研究

目的探讨核苷酸微阵列技术在复发性流产发病机制及潜在致病位点中的应用价值。方法选取2017年7月1日-2019年6月30日在深圳市罗湖区妇幼保健院妇产科门诊确诊为复发性流产的患者60例,均留取流产物样本。应用Affymetrix Cyto Scan HD探针对样本进行SNP array检测,通过Affymetrix Chromosome Analysis Suite软件采用隐马科夫模型算法确定全基因组染色体区域的重复和缺失。结果 60例研究标本检测成功率为100. 00%,共检测出44例样本异常,其中三倍染色体异常4例(6. 67%),染色体微小的缺失或重复3例(5. 00%),X染色体缺失8例(13. 33%),单亲二倍体1例(1. 67%),2号染色体重复1例(1. 67%),4号染色体重复1例(1. 67%),9号染色体重复1例(1. 67%),13号染色体重复2例(3. 33%),14号染色体重复1例(1. 67%),15号染色体重复1例(1. 67%),16号染色体重复10例(16. 67%),17号染色体重复1例(1. 67%),18号染色体重复2例(3. 33%),20号染色体重复1例(1. 67%),21号染色体重复4例(6. 67%),22号染色体重复3例(5. 00%)。其中年龄≥35岁患者的样本异常率为88. 89%(16/18),高于年龄≤35岁患者的66. 67%(28/42),差异有统计学意义(P>0. 05)。结论所有标本检测成功率达100. 00%,检出染色体异常率达73. 33%。染色体重复、缺失是复发性流产的主要原因,其中染色体数目异常,X染色体缺失,16号、21号和22号染色体异常为主要潜在致病位点。核苷酸微阵列技术可检测出染色体数目、结构异常以及染色体微小缺失,有助于全面了解复发性流产染色体异常状况,指导再次生育流产风险评估。

Application of nucleotide microarray in pathogenesis and potential pathogenic loci of recurrent abortion

Objective To explore the application value of nucleotide microarray technology in analyzing the pathogenesis and potential pathogenic sites of recurrent abortion. Methods From July 1,2017 to June 30,2019,60 cases of patients with recurrent abortion were selected as the study subjects,and all the samples of abortion products were taken from the outpatient department of Obstetrics and Gynecology of Luohu District Maternal and Child Health Hospital of Shenzhen City. Affymetrix Cyto Scan HD probe was used to detect the SNP array of the samples. Hidden Markov model algorithm was used to determine the repetition and deletion of the whole genome chromosome region by Affymetrix Chromosome Analysis Suite software. Results The detection success rate of 60 samples was 100%. 44 samples were found to be abnormal. Among them,4( 6. 67%) had triploid chromosome abnormalities,3( 5. 00%) had minimal chromosome deletion or duplication,8( 13. 33%) had X chromosome deletion,1( 1. 67%) had haploid diploid,1( 1. 67%) had chromosome 2 duplication,1( 1. 67%) had chromosome 4 duplication,1( 1. 67%) had chromosome 9 duplication. 2 cases( 3. 33%) had Chromosome 13 duplication,1 case( 1. 67%) had chromosome 14 duplication,1 case( 1. 67%) had chromosome 15 duplication,10 cases( 16. 67%) had chromosome 16 duplication,1 case( 1. 67%) had chromosome 17 duplication,2 cases( 3. 33%) had chromosome 18 duplication,1 case( 1. 67%) had chromosome 20 duplication,4 cases( 6. 67%) had chromosome 21 duplication and 3 cases( 5. 00%) had chromosome 22 duplication. The sample abnormality rate of 18 patients aged over 35 years was 88. 89%( 16/18),which was higher than 66. 67%( 28/42) of patients aged under 35 years( P > 0. 05). Conclusion The detection success rate was 100%. The rate of chromosome abnormality was 73. 33%. Chromosome duplication and deletion are the main causes of recurrent abortion. Among them,chromosome number abnormality,X chromosome deletion,chromosome 16,21 and 22 abnormalities are the main potential pathogenic sites. Nucleotide microarray technology can detect the true duplication of chromosome number,structure abnormality and minimal chromosome deletion duplication,which is helpful to understand the chromosome of recurrent abortion comprehensively and the risk assessment of the abnormal conditions to guide reproductive abortion again.