目的 染色体微阵列分析技术能在全基因组水平进行遗传分析，尤其对检测染色体组微小缺失、重复等具有突出优势。本研究旨在探讨CMA在胎儿超声心血管异常及DiGeorge综合征诊断中的临床应用。方法 采用SNP全基因组染色体微阵列分析技术（Affymetrix Cytoscan750K芯片）对本院2014至今的204例超声筛查出现心血管异常的胎儿进行检测。并筛出DiGeorge病例以及未有心血管异常的DiGeorge病例进行分析。样本包括产前的羊水、脐血、绒毛、引产组织。并对样本超声心血管异常进行单一心脏异常、多发心脏异常、心脏异常合并心外畸形进行分类。并用chas v3.1软件对结果进行分析。结果 204例心血管异常的样本中，产前诊断样本199例（97.55%），产后样本5例（2.45%）。产前产后DiGeorge异常诊断率分别为2.94%（6/204）和20%(1/5)。单一心脏结构异常71例（34.80%），多发心血管异常75例（36.76%），心血管异常合并心外异常58例（28.43%）；3组染色体微阵列分析技术结果显示DiGeorge异常率分别为0%（0/71)、4%(3/75)和6.89%(4/58)。CMA检测出染色体异常的胎儿有37例，异常检出率为18.14%，具有临床意义拷贝变异数变异30例（14.71%），其中非整倍体12例（4例21-三体综合征、3例18-三体综合征、1例13-三体综合征、1例8-三体综合征、2例69XXX、1例T21 MOS、1例T8 MOS），占总例数的5.88%。7例临床意义未明病例。总的DiGeorge病例有14例，其中204例心血管异常的胎儿标本中，CMA检测出DiGeorge胎儿7例，DiGeorge异常检出率为3.43%，7例均为微缺失。同时有7例不伴有心血管异常的DiGeorge病例，5例为微缺失，2例缺失与重复同时存在，所有检出CNVS均小于5Mb。结论 先天性心脏病（CHD）与DiGeorge综合征密切相关。与常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微小缺失、重复的检出率，有助于临床风险评估及遗传咨询。因此，对于产前超声提示心血管异常的胎儿，即使染色体核型正常，CMA也可能检出异常，对于产前超声提示心血管系统结构异常的胎儿建议行CMA检查。
Objective Chromosomal microarray analysis can scan at the whole genome level, and detect the number of chromosomes in the copy, especially for the detection of chromosome group of small deletions, repeat and so has a prominent advantage. This study was designed to investigate the clinical application DiGeorge screening CMA diagnosis and analysis of DiGeorge in cardiovascular ultrasound abnormalities. Method Using SNP whole genome chromosome microarray analysis （Cytoscan750K chip） in our hospital from 2014-2017 to date 204 cases of ultrasound screening abnormalities of the fetus were detected and screened DiGeorge cases, as well as no cardiovascular abnormalities DiGeorge cases were analyzed. Samples include prenatal amniotic fluid, umbilical cord blood, villi, postpartum, including peripheral blood, fetal heart blood, stillbirth tissue. And the samples were subjected to single cardiac abnormalities, multiple cardiac abnormalities, abnormal cardiac abnormalities and extracardiac malformations. And chas v3.1 software to analyze the results. Results Among the 204 cases of cardiovascular abnormalities, 199 cases (97.55%) were prenatal diagnosis samples and 5 cases (2.45%) were postpartum samples. The diagnostic rates of DiGeorge were 2.94% (6/204) and 20% (1/5) respectively. There were 71 cases (34.80%) of single cardiac abnormalities, 75 cases (36.76%) with multiple cardiovascular abnormalities, 58 cases (28.43%) with abnormal cardiovascular abnormality, and three groups of chromosome microarray analysis showed that DiGeorge abnormal rate was 0% (0/71), 4% (3/75), 6.89% (4/58) .There was significant difference between the three groups. There were 37 cases of fetal abnormalities detected by CMA, and the abnormal detection rate was 18.14%. There were 30 cases (14.71%) of mutations in clinical significance, 12 cases of aneuploidy (4 cases of 21 - trisomy syndrome, 3 cases of 18-trisomy syndrome, 1 case of 13-trisomy syndrome, 1 case of 8-trisomy syndrome, 2 cases of 69XXX, 1 case of T21 MOS, 1 case of T8 MOS), accounting for 5.88% of the total number of cases. 7 cases of clinical significance of unknown cases. There were 14 cases of total DiGeorge cases, of which 204 cases of cardiovascular abnormal fetal specimens, CMA detected DiGeorge fetus in 7 cases, DiGeorge abnormal detection rate of 3.43%, 7 cases were microdeletions. At the same time, there were 7 cases of DiGeorge with no cardiovascular abnormality, 5 cases were microdeletion, 2 cases were absent and repeated, and all detected CNVS were less than 5Mb. Conclusions Congenital heart disease is closely related to DiGeorge syndrome. Compared with the autosomal karyotype analysis technique, chromosome microarray analysis improves the detection rate of fetal minorities and repeated detection rate, which is helpful for clinical risk assessment and genetic counseling. Therefore, for ultrasound found that fetal cardiovascular abnormalities of pregnant women, in full informed of the circumstances, can choose CMA prenatal diagnosis.
