Zhang Jingjing, Ma Dingyuan, Wang Yan, Cao Li, Wu Yun, Qiao Fengchang, Liu An, Li Li, Lin Ying, Liu Gang, Liu Cuiyun, Hu Ping, Xu Zhengfeng
State Key Laboratory of Reproductive Medicine, Department of Prenatal Diagnosis, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, 123# Tianfei Street, Nanjing, 210029 China.
Department of Ultrasound, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, 123# Tianfei Street, Nanjing, 210029 China.
Mol Cytogenet. 2015 Dec 29;8:100. doi: 10.1186/s13039-015-0209-5. eCollection 2015.
Congenital heart defects (CHD) represent one of the most common birth defects. This study aimed to evaluate the value of multiplex ligation-dependent probe amplification (MLPA) as a tool to detect the copy number variations (CNVs) of 22q11 in fetuses with CHD.
A large cohort of 225 fetuses with CHD was screened by fetal echocardiography. Once common chromosome abnormalities in 30 fetuses were screened out by conventional G-banding analysis, the CNVs of chromosome 22q11 in the remaining 195 fetuses were determined by MLPA for prenatal genetic counseling. In 195 CHD fetuses with normal karyotype, 11 cases had pathological CNVs, including 22q11.2 deletion (seven cases), the deletion of 22q11 cat eye syndrome (CES) region (one case), 22q11.2 duplication (one case), 22q13.3 deletion (one case) and 17p13.3 deletion (one case). In total, our findings from MLPA screening represented 4.9 % in our cohort. Among these, three cases were inherited CNVs, and eight cases were de novo. These CNVs were further verified by single nucleotide polymorphism (SNP)-array analysis, and their chromosomal location was refined.
This study indicated that MLPA could serve as an effective test for routine prenatal diagnosis of 22q11 in fetuses with CHD.
先天性心脏病（CHD）是最常见的出生缺陷之一。本研究旨在评估多重连接依赖探针扩增技术（MLPA）作为检测先天性心脏病胎儿22q11拷贝数变异（CNV）工具的价值。
通过胎儿超声心动图对225例先天性心脏病胎儿进行了大规模队列研究。通过常规G显带分析筛查出30例胎儿常见染色体异常后，对其余195例胎儿采用MLPA检测22号染色体q11区域的CNV，用于产前遗传咨询。在195例核型正常的先天性心脏病胎儿中，11例存在病理性CNV，包括22q11.2缺失（7例）、22q11猫眼综合征（CES）区域缺失（1例）、22q11.2重复（1例）、22q13.3缺失（1例）和17p13.3缺失（1例）。总体而言，MLPA筛查结果在我们的队列中占4.9%。其中，3例为遗传性CNV，8例为新发。这些CNV通过单核苷酸多态性（SNP）阵列分析进一步验证，并精确确定了其染色体定位。
本研究表明，MLPA可作为先天性心脏病胎儿22q11常规产前诊断的有效检测方法。
