1317例高危孕妇胎儿产前分子细胞遗传学分析

Prenatal molecular cytogenetic analysis of 1 317 high-risk pregnancies

目的探讨染色体核型分析及单核苷酸多态性微阵列技术(SNP-Array)在高危孕妇胎儿中的产前诊断应用价值。方法回顾性研究1317例具有产前诊断指征的高危孕妇胎儿,孕妇年龄17~48周岁,孕周17~34周。行G显带核型分析联合SNP-Array检测,统计分析其染色体结果及妊娠结局。结果在1317例胎儿染色体中,核型多态性44例(3.3%),核型异常152例(11.5%),SNP-Array异常241例(18.3%),两种检测比较差异有统计学意义。两种检测联合应用染色体异常270例(20.5%),与核型异常检出率比较差异均有统计学意义。核型与SNP-Array均异常123例(9.3%),核型正常中SNP-Array异常110例(9.8%),SNP-Array正常中核型异常31例(2.9%)。剔除其他指标干扰,在孤立性指标中,孤立性无创高危组的胎儿核型和SNP-Array异常率最高。合并两类指标中,高龄仅合并无创高危组的胎儿核型及SNP-Array异常率最高。21-三体发生率与年龄呈正相关(P=0.037)。在不良孕史中,孤立性胎停育史组的胎儿核型异常率最高,其他不良孕史合并超声软指标阳性组SNP-Array异常率最高。在孤立性超声软指标阳性分组中,核型分析仅孤立性心内强回声灶的胎儿检出染色体异常,SNP-Array检测孤立性NF增厚的胎儿染色体异常率最高,其次依次是孤立性长骨短、孤立性侧脑室扩张。剔除其他指征仅超声异常者,随超声异常数目增多,核型和SNP-Array异常率随之升高,差异有统计学意义。结论21-三体发生率与年龄呈正相关,无创高危、胎停育史、长骨短、NF增厚和侧脑室扩张提示染色体异常风险升高,心内强回声灶仍不排除染色体异常的可能,遗传咨询中双亲验证后的家系综合分析仍十分重要,核型分析联合SNP-Array技术可提高染色体异常检出率,核型结果与SNP-Array结果相互补充,可以更精准地分析染色体异常,有利于遗传咨询及再生育指导,是高危孕妇胎儿首选的产前诊断方案。

Objective To investigate the value of chromosome karyotype analysis and single nucleotide microarray(SNP-array)in prenatal diagnosis of high-risk pregnant fetuses.Methods A retrospective study was conducted among 1317 high-risk pregnant women and fetuses with prenatal diagnosis indication.The pregnant women were 17-48 years old,and the gestational ages were 17-34 weeks.Analysis on G banding karyotype and single nucleotide microarray(SNP-array)technique were performed,chromosome results and pregnancy outcomes were collected and analyzed.Results Among 1317 fetal chromosomes,there were 44 cases(3.3%)of karyotype polymorphism,152 cases(11.5%)of karyotype abnormality,and 241 cases(18.3%)of SNP-array abnormality.There was significant differences between the two tests.There were 270 cases(20.5%)of chromosomal abnormalities using both G banding karyotype and SNP-array technique,and there was statistically significant differences with the detection rate of karyotype abnormalities.There were 123 cases(9.3%)with abnormal karyotype and SNP-array,110 cases(9.8%)with abnormal karyotype,and 31 cases(2.9%)with abnormal karyotype.After excluding the interference of other indicators,the incidence of fetal karyotype and SNP-array abnormality was the highest in the isolated non-invasive high-risk group.Among the two types of combined indicators,fetal karyotype and SNP-array abnormality rate were highest in the elderly high-risk group with only non-invasive combination.The incidence of trisomy 21 was positively correlated with age(P=0.037).Among the adverse pregnancy history,the group with isolated abortive history had the highest rate of abnormal fetal karyotype,and the group with other adverse pregnancy history combined with positive soft ultrasound index had the highest rate of abnormal SNP-array.The chromosomal abnormalities were highest in fetuses with isolated NF thickening detected by SNP-ARRAY,followed by isolated long bone shortening and isolated lateral ventricular dilation.When the number of ultrasound abnormalities increased,the rate of karyotype and SNP-array abnormalities increased with the exclusion of other indicators but only ultrasound abnormalities,and the difference was statistically significant.Conclusion The incidence of trisomy 21 is positively correlated with age,Indication of non-invasive high risk,history of embryo arrest,short bone length,NF thickening and lateral ventricle dilation suggest increased risk of chromosomal abnormalities.The possibility of chromosomal abnormalities cannot be ruled out by intracardiac hyperechoic foci.Comprehensive pedigree analysis family after parental verification is still very important in genetic counseling.Karyotype analysis combined with SNP-ARRAY technology can improve the detection rate of chromosomal abnormalities.It′s complementary to conduct karyotype and SNP-array analysis which would provide more accurate analysis for chromosomal abnormalities.Genetic counseling and reproductive guidance would benefit from the combined test and it is the preferred prenatal diagnosis program for fetuses of high-risk pregnant women.