SNP-array分析在颈项皮肤皱褶增厚胎儿遗传学诊断中的应用

  目的  探讨胎儿颈部皮肤皱褶(nuchal fold，NF)增厚的产前诊断与遗传咨询。  方法  回顾性分析2018年1月—2019年8月间来广西壮族自治区妇幼保健院产科产检，超声检查提示孕中期16~18孕周NF≥5.0 mm；19~22孕周NF≥6.0 mm的152例NF增厚的孕妇，行羊膜腔穿刺抽取羊水标本，同时行羊水细胞核型分析和染色体微阵列芯片技术(single nucleotide polymorphism array，SNP-array)检测，统计这些孕妇的临床诊断资料，并分析胎儿染色体核型分析与染色体微阵列芯片检测结果。  结果  152例NF增厚胎儿标本中，检出染色体核型异常19例，检出率为12.5%(19/152)。19例异常核型中21-三体:12例；18-三体:2例；45，X:2例；47，XXX:1例；嵌合体45, -628]/46, r(6)(p25q26)12]:1例；46, XN, del(5)(p14):1例。SNP-array检出33例异常，检出率为21.71%(33/152)，SNP-array技术的检出率明显高于核型分析的异常检出率。除了能检出核型分析发现的染色体非整倍体或大片段结构异常外，SNP-array技术还检出染色体核型分析未能检出的14例微缺失，其中4例致病性拷贝数变异，2例可疑致病性拷贝数变异，其余8例为临床意义不明拷贝数变异病例。  结论  对超声筛查为胎儿颈背皮肤皱褶增厚的病例，SNP-array技术诊断可明显提高染色体核型分析未能检测出的染色体亚显微结构的畸变。 

Application of single nucleotide polymorphism microarray in genetic diagnosis of nuchal fold thickened fetuses

Objective To discuss the prenatal diagnosis and genetic counseling of nuchal fold(NF) thickened fetuses. Methods A retrospective analysis was performed on 152 pregnant women with NF ≥ 5.0 mm at 16-18 gestational weeks and NF ≥ 6.0 mm at 19-22 gestational weeks From January 2018 to July 2019 in Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region. Amniotic fluid samples were obtained by amniocentesis, and chromosome karyotype analysis and single nucleotide polymorphism array(SNP-array) were performed at the same time. Clinical diagnostic data of these pregnant women were collected, and fetal chromosome karyotype analysis and chromosome microarray detection results were analyzed. Results Among the 152 cases of nuchal fold thickened fetuses, 19 cases(19/152, 12.5%) of chromosomal karyotype abnormalities were detected. Among the 19 abnormal karyotypes, there were 12 cases of trisomy 21, 2 cases of trisomy 18, 2 cases of 45, X, 1 cases of 47, XXX, 1 cases of 45,-628]/46, r(6)(p25 q26)12], and 1 case of 46, XN, del(5)(p14). There were 33 abnormal cases detected by SNP-array, with a detection rate of 21.71%(33/152). The SNP-array detection rate was significantly higher than that of chromosome karyotype. In addition to the aneuploid or large fragment structural abnormalities detected by karyotype detection, the SNP-array also detected 14 cases of microdeletions not detected by karyotype analysis, including 4 cases of pathogenic copy number variation, 2 cases of suspected pathogenic copy number variation, and 8 cases of unknown clinical significance copy number variation. Conclusion For the nuchal fold thickened fetuses screened by ultrasound, SNP array technique can significantly improve the chromosome ultrastructure aberrations which cannot be detected by karyotype analysis.