Effects of subtelomeric copy number variations in miscarriages

Abstract

Purpose: This study was performed on miscarriage samples for chromosome analysis to detect copy number variations (CNVs) related to subtelomeric regions, and with these results we aimed to adapt multiplex ligation-dependent probe amplification (MLPA) method for prenatal diagnosis.

Materials and methods: The cell cultures and DNA isolations were performed on 60 miscarriage samples. For maternal contamination analysis, DNA isolations and quantitative fluorescent polymerase chain reactions were done using peripheric blood of mothers who had miscarriages. We compared short tandem repeat peak profiles of miscarriage samples and mothers. The subtelomeric regions of the chromosomes were assessed using the MLPA method.

Results: Of 43 miscarriage samples, 19 had normal karyotype (44.2%), 10 had numerical abnormalities (23.3%), and 2 had structural abnormalities (4.7%). Subtelomeric 16q duplication was determined in 2 of the 30 miscarriage samples investigated with MLPA method (6.6%).

Conclusion: There is no statistically significant difference between two groups (p > 0.05). However, the fact that the 6.6% subtelomeric CNV found in miscarriage samples was not found in controls, showed that further studies are required. We recommend that the miscarriage samples of the couples with recurrent miscarriage should be analyzed in terms of subtelomeric CNV after the exclusion of other clinical reasons.

Chinese abstract

目的：通过对流产物取样进行染色体分析来检测端粒近端区域基因拷贝数异变（CNVs）情况，旨在将多重连接探针扩增技术（MLPA）用于产前诊断。

材料与方法：对60例流产物样本进行细胞培养和DNA分离。采用母体外周血进行母体细胞污染分析、DNA分离及荧光定量聚合酶链反应。我们比较了流产样本和母血中短串联重复序列峰值情况。采用MLPA对染色体亚端粒区进行评估。

结果：43例流产样本中，19例核型正常（44.2%）。10例染色体数目异常（23.3%）2例结构异常（4.7%）。采用MLPA对30例流产样本进行检测，其中2例发生端粒区域16号染色体长臂复制（6.6%）。

结论：两组没有明显的统计学差异（p>0.05）。然而流产样本中发现6.6%端粒近端区域基因拷贝数异变，而控制组中没有发现，尚需进一步研究。我们建议对于存在复发性流产的夫妇在排除其他临床原因外应对流产物样本进行端粒近端区域基因拷贝数异变分析。

• Infertility
• pregnancy
• urogenital system

Declaration of interest

The authors declare no conflict of interest. This study was supported by Ondokuz Mayis University Research Foundation (PYO.TIP.10043).