Gajjar Kinjal, Patel Alpesh, Patel Bhikhabhai, Chettiar Shiva, Jhala Devendrasinh
K Gajjar, Department of Zoology, Gujarat University, Ahmedabad, India.
A Patel, GeneXplore Diagnostics and Research Centre Pvt. Ltd., Ahmedabad, India.
Reprod Fertil. 2023 Mar 1;4(2). doi: 10.1530/RAF-22-0092.
To evaluate the proportion of chromosomal abnormalities in recurrent pregnancy loss (RPL) assisted by array comparative genomic hybridization (aCGH) bright out with higher detection rate, more accuracy, and less sample failure as compared with conventional cytogenetic analysis. In this study, product of conception samples with abnormal USG findings of the fetus and clinical history of RPL were first processed for karyotyping and Fluorescence In Situ Hybridization analysis. Normal results given by Karyotype and FISH samples with major anomalies detected by Ultrasound with RPL were divided into six groups and aCGH was performed to detect the gain or loss and copy number variations (CNVs) of a particular gene present in chromosomal segments. Among a total of 300 POC samples, 100 abnormal samples were identified either by karyotype (n=70) or by FISH (n=30). From the remaining 200 samples, 5 showed the presence of maternal cell contamination excluded. aCGH analysis revealed (n=195) that 74 (38%) samples with copy number variations (CNVs) and two samples with variants of unknown clinical significance (VOUS) were clinically associated with the clinical findings and 121(62%) samples showed no change in CNVs. The most frequent CNVs were loss of chromosome regions at 2q33.1, 7q11.21, 15q11.1, 16p11.2, Xp22.33, and Yp11.32. CNVs at arr[GRCh37]7p22.3,p21.2(830852-15124702)×1,7q34q36.3(141464180_158909738)×3, 14.2Mbp deletion of 7p22.3p21.2 (SUN1 gene) and 17.4Mbp duplication of 7q34q36.3 (KCNH2, CNTNAP2, and SHH genes) in one sample, CNVs at arr[GRCh37]8p22.2q22.3 (86326349_105509986)×1, 2.48Mbp deletion of 8p22.2q22.3 (GRHL1 gene) were found in another sample.
为评估与传统细胞遗传学分析相比，采用比较基因组杂交芯片（aCGH）辅助复发性流产（RPL）时染色体异常的比例，结果显示其检测率更高、准确性更高且样本失败率更低。在本研究中，首先对胎儿超声检查结果异常且有RPL临床病史的妊娠产物样本进行核型分析和荧光原位杂交分析。核型分析和荧光原位杂交结果正常且超声检查发现有主要异常以及有RPL的样本被分为六组，并进行aCGH检测，以检测染色体片段中特定基因的增减和拷贝数变异（CNV）。在总共300份妊娠产物样本中，通过核型分析（n = 70）或荧光原位杂交（n = 30）鉴定出100份异常样本。在其余200份样本中，排除了5份存在母血细胞污染的样本。aCGH分析显示（n = 195），74份（38%）有拷贝数变异（CNV）的样本和2份临床意义不明变异（VOUS）的样本与临床发现相关，121份（62%）样本的CNV无变化。最常见的CNV是2q33.1、7q11.21、15q11.1、16p11.2、Xp22.33和Yp11.32染色体区域的缺失。在一个样本中发现arr[GRCh37]7p22.3,p21.2(830852 - 15124702)×1、7q34q36.3(141464180_158909738)×3、7p22.3p21.2（SUN1基因）14.2Mbp缺失以及7q34q36.3（KCNH2、CNTNAP2和SHH基因）17.4Mbp重复的CNV，在另一个样本中发现arr[GRCh37]8p22.2q22.3(86326349_105509986)×1、8p该文档中未提及的内容，无法准确翻译。22.2q22.3（GRHL1基因）2.48Mbp缺失的CNV。
