2021 年第 12 期 第 16 卷

胎儿超声指标异常的遗传病因学分析

Genetic etiology analysis of fetal ultrasound abnormalities

作者：陈梅1张帅2查斌斌2范晓宇2李毅2

英文作者：Chen Mei1 Zhang Shuai2 Zha Binbin2 Fan Xiaoyu2 Li Yi2

单位：1山东国欣颐养集团华丰医院妇产科，山东省泰安市271413;2山东省泰安市中心医院检验科271000

英文单位：1Department of Obstetrics and Gynecology Huafeng Hospital of Shandong Guoxin Yiyang Group Shandong Province Taian 271413 China; 2Department of Clinical Laboratory Taian City Central Hospital Shandong Province Taian 271000 China

关键词：胎儿超声；侵入性产前诊断；染色体核型；染色体微阵列分析

英文关键词：Fetalultrasound;Invasiveprenataldiagnosis;Chromosomekaryotype;Chromosomemicroarrayanalysis

• 摘要：

• 目的 从细胞和分子水平探讨胎儿超声异常的遗传病因学反映。方法 选取2004年6月至2019年7月山东省泰安市中心医院以胎儿超声指标异常为指征进行侵入性产前诊断的病例302例，对其染色体及微阵列检查结果  进行回顾性总结分析。结果  302例超声指标异常胎儿中，检出染色体核型异常62例，检出率20.5%。不同超声指标异常项染色体异常检出率依次为：结构畸形合并软指标异常33.3%（4/12）＞软指标异常27.2%（40/147）＞结构畸形15.8%（9/57）；胎儿颈部淋巴水囊瘤病例染色体异常检出率最高，为58.3%（7/12），其次为颈项透明层增厚，异常核型检出率为38.4%（28/73）。合并3项及以上软指标异常组中，胎儿染色体异常检出率高于单纯1项组［36.4%（4/11）比26.5%（35/132）］，差异有统计学意义（χ2=0.441，P=0.543）。21-三体、性染色体异常及18-三体是最常见的超声异常胎儿的染色体异常类型。高龄孕妇组染色体异常检出率高于低龄孕妇组（P<0.05）。65例同时进行染色体核型及染色体微阵列分析(CMA)的胎儿中，核型正常而CMA异常13例，其中6例为致病性微缺失微重复综合征。结论  孕早中期超声筛查有助于更早地检出染色体异常胎儿，超声指标异常种类和数量越多及孕妇高龄合并胎儿超声指标异常时，发生染色体异常的概率增高；颈项透明层增厚、颈部淋巴水囊瘤等指标对染色体异常有重要提示价值，CMA在分子水平对染色体核型分析提供有力补充。

• Objective To explore the genetic etiological reflection of fetal ultrasound abnormalities at cellular and molecular levels. Methods From June 2004 to July 2019, 302 cases of invasive prenatal diagnosis with fetal ultrasound abnormalities in Taian City Central Hospital, Shandong Province were selected. The results of chromosome and microarray examination were retrospectively analyzed. Results In 302 cases of fetal ultrasound abnormalities, there were 62 cases of chromosomal karyotype abnormalities, and the total abnormal detection rate was 20.5%. The detection rates of fetal chromosomal abnormalities under different ultrasonic indexes abnormal items were as follows: structural deformity combined with soft index abnormality 33.3%(4/12)＞soft index abnormality 27.2%(40/147)＞structural deformity 15.8%(9/57). The highest detection rate of chromosomal karyotype abnormality in fetal cervical lymphangioma was 58.3%(7/12), followed by 38.4%(28/73) in cervical hyaline layer thickening. In the three or more soft index abnormalities group, the detection rate of fetal chromosomal abnormalities was higher than that in only one soft index abnormality group［36.4%（4/11） vs 26.5%（35/132）］(χ2=0.441, P=0.543). Trisomy 21, sex chromosome abnormalities and trisomy 18 were the most common chromosomal abnormalities in fetal ultrasound abnormalities. The detection rate of chromosomal abnormalities in elderly pregnant women was higher than that in young pregnant women(P<0.05). There were 65 cases detected by chromosome karyotype and chromosome microarray analysis at the same time, including 13 cases with normal karyotype but abnormal chromosome microarray analysis, of which 6 cases had pathogenic microdeletion and microduplication syndrome. Conclusions   Ultrasound screening in the first and second trimester of pregnancy is helpful to detect fetal chromosomal abnormalities earlier, the more types and numbers of ultrasound abnormalities and the higher the age of pregnant women with fetal ultrasound abnormalities, the higher the probability of chromosomal abnormalities. The ultrasonic indexes such as cervical hyaline layer thickening and cervical lymphangioma are important value to indicate chromosome abnormality. Chromosomal microarray analysis provides a powerful complement to karyotype analysis at the molecular level.