伴染色体异常的48例无精子症患者基因组拷贝数变异分析

Analysis of genomic copy number variation in 48 azoospermia patients with chromosomal abnormalities

目的:分析伴染色体异常的无精子症患者基因组拷贝数变异(CNV)情况。方法:选取2018年10月—2022年3月就诊于银川市妇幼保健院的204例无精子症患者,采用G显带核型分析技术分析染色体核型;采用二代测序技术(NGS)检测基因组CNV情况,筛选出基因组CNV相关基因,综合参考人类基因组hg19版本、基因组变异数据库、人类染色体不平衡和表型数据库、在线人类孟德尔遗传数据库、加利福尼亚大学圣克鲁兹分校数据库及PubMed等公共数据库的最新公布数据而确定。所有数据录入Excel表中,统计分析各指标的构成比和(或)百分率。结果:204例无精子症患者中,48例出现染色体异常,发生率为23.53%,其中构成比>5%的依次为47,XXY(47.92%)、46,X,Yqh-(12.50%)、46,XY,16qh+(6.25%);48例染色体异常患者中,42例存在基因组CNV,其中存在1个基因组CNV的27例,存在2个基因组CNV的11例,存在3个基因组CNV的2例,存在4个基因组CNV的2例,构成比>5%的依次为X染色体(39.68%)、Y染色体(14.29%)、11号染色体(6.35%)和15号染色体(6.35%);63个基因组CNV中,片段大小0.10~2.38 Mb,共检出相关基因90个,其中缺失26个、重复64个。结论:通过G显带核型分析联合NGS检测,可以为无精子症患者提供更为完整的遗传学评估。

Objective To analyze the copy number variation(CNV)of genome in azoospermia patients with chromosomal abnormalities.Methods A total of 204 patients with azoospermia treated in Maternal and Child Health Hospital of Yinchuan from October 2018 to March 2022 were selected to analyze the karyotype of chromosomes by G banding karyotype analysis.The next generation sequencing technology(NGS)was used to detect genomic CNV,screen out genomic CNVs related genes,and determine by referring to the latest published data of Human Genome hg19 version,Database of Genomic Variants,Database of Chromosomal Imbalance and Phenotype in Humans Using Ensemble Resources,Online Mendelian Inheritance in Man,University of California Santa Cruz database,PubMed and other public databases.All data were entered into Excel table,and the composition ratio and(or)percentage of each indicator were statistically analyzed.Results Among the 204 patients with azoospermia,48 patients(23.53%)had chromosomal abnormalities,of which 47,XXY(47.92%),46,X,Yqh-(12.50%),46,XY,16qh+(6.25%)composition ratio for more than 5%.Chromosome abnormalities were found in 48 patients,including 42 patients with genomic CNV,including 27 patients with 1 genomic CNV,11 patients with 2 genomic CNVs,2 patients with 3 genomic CNVs,and 2 patients with 4 genomic CNVs.The X chromosome(39.68%),Y chromosome(14.29%),chromosome 11(6.35%),and chromosome 15(6.35%)composition ratio for more than 5%of the total.Among the 63 genomic CNVs,the fragment size was 0.10-2.38 Mb,and 90 related genes were detected,including 26 deletions and 64 repeats.Conclusions G-banding karyotype analysis combined with NGS detection can provide more complete genetic evaluation for azoospermic patients.