Liu Yanyan, Zhu Hongmei, Zhang Xuan, Hu Ting, Zhang Zhu, Wang Jing, Lai Yi, Zheng Jiemei, Xie Dan, Xia Bei, Qin Li, Xie Liangyu, Liu Shanling, Wang He, Sun Huaqin
Prenatal Diagnosis Center, Department of Obstetrics & Gynecologic, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China.
SCU-CUHK Joint Laboratory for Reproductive Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China.
Mol Genet Genomic Med. 2018 Nov;6(6):1249-1254. doi: 10.1002/mgg3.487. Epub 2018 Nov 20.
A 30-year-old oligoasthenozoospermia man was found to have unbalance mosaic translocation between chromosome 22 and four other chromosomes (5, 6, 13, and 15) during the investigations for a couple with infertility for 3 years, which is a rare event in human pathology.
Classical cytogenetics analysis, fluorescence in situ hybridization (FISH), and chromosome microarray analyses (CMA) were performed on peripheral blood lymphocytes; copy number variation sequencing (CNV-Seq) analysis was performed on sperm DNA.
Classical cytogenetics analysis showed the presence of six cell lines on peripheral blood lymphocytes: 45, XY, der (13) t(13;22),-22[10]/46, XY, t(13;22)[6]/45, XY, der(15)t(15;22),-22[4]/46, XY, t(13;22)[1]/45, XY, der(5)t(5;22),-22[1]/45, XY, der(6)t(6;22)[1]. FISH and CMA performed on peripheral blood cells showed the presence of a 6.9 Mb mosaic 22q11 deletion (approximately 50% of cells); it is unexpected that the phenotypes of this man were merely oligoasthenozoospermia, mild bradycardia, and mild tricuspid regurgitation. CNV-Seq analysis performed on sperm DNA revealed the rate of 22q11 deletion cells was obviously lower compared with peripheral blood cells. And the frequency of gametes exhibiting a normal or balance chromosomal equipment was above 80% in sperm samples.
To the best of our knowledge, this report is the first case of a de novo gonosomal mosaic of chromosome 22q11 deletion just associated with male infertility.
在对一对不育夫妇进行为期3年的调查过程中,发现一名30岁的少弱精子症男性存在22号染色体与其他四条染色体(5号、6号、13号和15号)之间的不平衡嵌合易位,这在人类病理学中是罕见事件。
对外周血淋巴细胞进行经典细胞遗传学分析、荧光原位杂交(FISH)和染色体微阵列分析(CMA);对精子DNA进行拷贝数变异测序(CNV-Seq)分析。
经典细胞遗传学分析显示外周血淋巴细胞存在六种细胞系:45,XY,der(13)t(13;22),-22[10]/46,XY,t(13;22)[6]/45,XY,der(15)t(15;22),-22[4]/46,XY,t(13;22)[1]/45,XY,der(5)t(5;22),-22[1]/45,XY,der(6)t(6;22)[1]。对外周血细胞进行的FISH和CMA显示存在6.9Mb的22q11嵌合缺失(约50%的细胞);出乎意料的是,该男性的表型仅为少弱精子症、轻度心动过缓和轻度三尖瓣反流。对精子DNA进行的CNV-Seq分析显示,22q11缺失细胞的比例明显低于外周血细胞。精子样本中染色体组成正常或平衡的配子频率高于80%。
据我们所知,本报告是首例与男性不育相关的22q11染色体新发性染色体嵌合病例。