CNV-seq結合染色體核型分析技術在產前診斷胎兒染色體異常中的價值觀察

［摘 要］目的 探討基因組拷貝數變異測序（CNV-seq）結合染色體核型分析技術在產前診斷胎兒染色體異常中的價值。方法 回顧性選取2019年6月至2022年6月于綿陽市人民醫院產前診斷科行羊膜腔穿刺術且拷貝數變異（CNV）提示異常的107例孕婦為研究對象，分別行CNV-seq檢測和染色體核型分析。結果 在107例孕婦的羊水樣本中，染色體核型分析檢出58例（54.21%）胎兒核型異常，包括染色體數目異常36例（62.07%），染色體結構異常11例（18.97%），嵌合體11例（18.97%）。CNV-seq檢測對染色體核型分析中的58例核型異常者均成功確診，變異類型包括54例（93.10%）致病性，4例（6.90%）臨床意義不明；CNV-seq檢出13例嵌合體病例，其中2例（低于10%）染色體核型分析未檢出。在49例核型未見異常羊水樣本中，CNV-seq檢出致病性變異類型20例（40.82%）、臨床意義不明23例（46.94%）、可能良性2例（4.08%）、可能致病性1例（2.04%）、良性變異3例（6.12%）。染色體核型分析產前診斷胎兒染色體異常的陽性率均明顯低于CNV-seq檢測及二者聯合檢測的陽性率（χ2=115.654，P＜0.05）；三種檢測方法產前診斷胎兒染色體數目異常、染色體結構異常和嵌合體的檢出率比較差異均無統計學意義（P＞0.05）。結論 在胎兒染色體異常的產前診斷中，CNV-seq可高效、特異地檢出染色體核型分析技術無法檢出的致病性基因組CNVs，可為產前遺傳咨詢提供更詳細的參考信息。

［關鍵詞］基因組拷貝數變異測序；染色體核型分析；染色體異常；產前診斷

Doi：10.3969/j.issn.1673-5293.2024.08.010

［中圖分類號］R174""" ［文獻標識碼］A

［文章編號］1673-5293（2024）08-0069-07

Value of CNV-seq combined with karyotype analysis in prenatal diagnosis of fetal chromosome abnormalities

ZHONG Lijuan1，CHEN Yan2，ZHONG Rong1，CHEN Pan3，HE Xia3，WANG Lijun3，TANG Shuang3

（1.Department of Obstetrics and Gynecology，Chongqing Maternal and Child Health Hospital，

Women and Children’s Hospital Affiliated with Chongqing Medical University，Chongqing 401147，China;

2.Department of Ultrasound，Mianyang People’s Hospital，Sichuan Mianyang 621000，China;

3.Department of Prenatal Diagnosis，Mianyang People’s Hospital，Sichuan Mianyang 621000，China）

［Abstract］ Objective To investigate the value of genome copy number variation sequencing （CNV-seq） combined with karyotype analysis technology in prenatal diagnosis of fetal chromosome abnormalities. Methods A retrospective study was conducted on 107 pregnant women who underwent amniocentesis and were indicated to have copy number variation （CNV） from June 2019 to June 2022 at the department of prenatal diagnosis，Mianyang People’s Hospital.All participants underwent both CNV-seq testing and karyotype analysis. Results In the amniotic fluid samples of 107 pregnant women，karyotype analysis identified 58 cases （54.21%） of fetal karyotype abnormalities，including 36 cases （62.07%） of numerical abnormalities，11 cases （18.97%） of structural abnormalities and 11 cases （18.97%） of mosaicism.CNV-seq testing successfully confirmed all 58 karyotype abnormalities identified by karyotype analysis.Among these，54 cases （93.10%） were pathogenic，and 4 cases （6.90%） had unknown clinical significance.Additionally，CNV-seq detected 13 cases of mosaicism，including 2 cases （less than 10%） that were not detected by karyotype analysis.In the 49 amniotic fluid samples with normal karyotypes，CNV-seq identified 20 cases （40.82%） of pathogenic variants，23 cases （46.94%） of variants of unknown clinical significance，2 cases （4.08%） of likely benign variants，1 case （2.04%） of likely pathogenic variants and 3 cases （6.12%） of benign variants.The positive rate of fetal chromosomal abnormalities using karyotype analysis was significantly lower than that of CNV-seq and the combined testing method （χ2=115.654，P＜0.05）.There were no statistically significant differences in the detection rates for chromosomal numerical abnormalities，structural abnormalities，and mosaicism among the three testing methods （P＞0.05）. Conclusion In the prenatal diagnosis of fetal chromosome abnormalities，CNV-seq can effectively and specifically detect pathogenic genomic CNVs that cannot be identified by karyotype analysis.This provides more detailed reference information for prenatal genetic counseling.

［Key words］ genome copy number variation sequencing;karyotype analysis;chromosome abnormality;prenatal diagnosis

染色體結構及數目異常是臨床常見的染色體異常類型，與胎兒流產、新生兒出生缺陷密切相關，約占遺傳因素的80%以上［1-2］。……