耿娟 赵馨 王逾男 卢建 郭莉 黄伟伟 陈汉彪 何天文 尹爱华*

(1.广州医科大学附属广东省妇儿医院，广东 广州 511442；2.广东省妇幼保健院 医学遗传中心，广东 广州 510010)

心血管系统异常胎儿的染色体微阵列分析

耿娟1赵馨2王逾男2卢建2郭莉2黄伟伟2陈汉彪2何天文2尹爱华2*

(1.广州医科大学附属广东省妇儿医院，广东 广州 511442；2.广东省妇幼保健院 医学遗传中心，广东 广州 510010)

目的 探讨染色体微阵列分析技术在产前超声提示为先天性心脏病胎儿中的遗传学诊断价值。方法 收集154例因产前超声诊断为先天性心脏病的胎儿，取其羊水或脐血行染色体微阵列分析，其中111例病例同时行染色体核型分析。并根据单一心脏结构畸形、多发心脏结构畸形不合并心外畸形、心内合并心外畸形分为3组。结果 154例行染色体微阵列检测的胎儿中，37例结果异常，总致病性拷贝数变异的检出率为24.03%；111例核型分析结果中，共检测到13例异常结果，核型异常检出率为11.71%，两者差别有统计学意义(P=0.029)。 单一心脏结构畸形组50例，多发心血管系统异常组57例，心内合并心外畸形组47例。3组染色体微阵列分析结果异常率分别为2%(1/50)、31.58%(18/57)、38.30%(18/47)，3组差异有统计学意义(P<0.001)。3组染色体异常率分别为0%(0/39)、10.53%(4/38)、26.47%(9/34)，3组差异有统计学意义(P=0.002)。结论 先天性心脏病与微重复/微缺失综合征密切相关。与常规染色体核型分析技术相比，染色体微阵列分析技术提高了先天性心脏病胎儿染色体畸变的检出率，有助于临床风险评估及遗传咨询。

染色体微阵列分析技术；先天性心脏病；产前诊断；染色体拷贝数变异

Objective To investigate the value of chromosomal microarray analysis(CMA) in the fetuses with congenital heart disease(CHD) detected by ultrasound. Method 154 fetuses with abnormal ultrasound imaging’s were enrolled in this study, invasive prenatal diagnosis surgeries were performed at Guangdong Women and Children Hospital .All cases were screened for copy number variations (CNVs) and chromosome karyotype analysis was performed in 111 of the 154 prenatal samples. All samples were divided into three groups, Group Ⅰ:samples with isolated cardiac structural abnormalities; Group Ⅱ：cases with multiple cardiovascular abnormalities ; Group Ⅲ：cases of cardiovascular abnormalities complicated with other systemic abnormalities.Results Among the 154 pregnancies with CHD ,CMA revealed a CNVs abnormality in 37(24.03%), among the 111 fetal karytopes,21 (18.92%) were chromosomal abnormality (P=0.368).Three groups contained 50 ,57 ,47 cases respectively. The abnormal CNVs detection rate among the 3 groups were 2%(1/50)、31.58%(18/57)、38.30%(18/47), respectively(P<0.001),while the chromosomal abnormalities were 2.41%(4/39)、15.79%(6/38)、32.35%(11/34), respectively(P=0.046). Conclusions Conclusions CHD is closely associated with abnormal CNVs and chromosomal abnormalities. Compared with the conventional karyotyping techniques, CMA improves the detection rate of chromosomal aberration in CHD, and is helpful for assess the risk and conduct the genetic counseling.【Key words】 chromosomal microarray analysis；congenital heart disease；prenatal diagnosis；copy number variations

先天性心脏病(congenital heart disease，CHD)是最常见的出生缺陷之一，也是导致婴儿发病和死亡的首要病因[1, 2]，在活产儿中的发病率为8‰～9‰[3]。研究表明，CHD主要受遗传因素和环境因素的相互作用[4-6]，其中遗传因素包括非整倍体染色体、染色体重排、染色体微缺失/微重复[7, 8]。……