染色体微阵列分析在超声软指标产前诊断中的应用价值
|
摘要
目的探讨染色体微阵列分析技术(CMA)在超声软指标异常胎儿产前诊断中的临床应用价值及染色体拷贝数变异(CNVs)与超声软指标异常的相关性。方法选取2015年1月～2018年3月于我院就诊并接受介入性产前诊断的超声检查发现软指标异常且未合并明确结构异常的421例病例,所有病例均采用美国Affymetrix公司的CytoScan 750k芯片进行CMA检测及常规方法进行G显带染色体核型分析,根据相关生物信息学数据库对CMA检测结果进行全面分析,定期复查胎儿的发育情况,随访妊娠结局及胎儿出生后的生长发育状况。结果 421例超声软指标异常患者中,29例检出明确致病性染色体异常(6.9%),其中染色体非整倍体占4.0%,致病性CNVs占2.9%。340例为单一软指标异常,检出明确致病性染色体异常21例(6.2%);81例为合并两项或以上超声软指标异常,检出明确致病性染色体异常8例(9.9%),两组差异有统计学意义(P<0.05)。不同部位的超声软指标异常胎儿染色体异常检出率:颈项透明层(NT)增厚或颈后皮肤皱褶(NF)增厚中检出明确致病性染色体异常6例(21.4%),脉络丛囊肿中检出明确致病性染色体异常2例(5.8%),侧脑室扩张中明确致病性染色体异常4例(5.5%),鼻骨发育不良中检出明确致病性染色体异常3例(11.1%),心室强光点中检出明确致病性染色体异常1例(1.6%),肾盂分离中未检出明确致病性染色体异常,肠管回声增强中检出明确致病性染色体异常2例(8.7%),股骨短小中检出明确致病性染色体异常2例(5.7%),单脐动脉中检出明确致病性染色体异常1例(3.7%)。结论妊娠中晚期超声软指标两项及以上异常、鼻骨缺失或发育不良及NT或NF增厚、侧脑室扩张、肠管回声增强胎儿中的染色体异常检出率相对较高,对合并这些软指标的胎儿进行介入性产前诊断非常必要。CMA可有效地检出染色体非整倍体及具有临床意义的微缺失或微重复,从而显著提高超声软指标异常胎儿染色体异常的检出率,可有效降低胎儿出生缺陷的发生。
Objective To explore the application value for fetuses with ultrasonographic soft markers by genome-wide high resolution chromosomal microarray analysis(CMA) and investigate the relationship between Chromosome abnormalities and ultrasonographic soft markers. Methods 421 pregnant women with ultrasonographic soft markers without obvious structural abnormalities at the First Affiliated Hospital of AFMU(Air Force Medical University) from January 2015 to March 2018 were involved in the present study. All pregnant women performed invasive prenatal diagnosis. Microarray testing was performed using Affymetrix CytoScanTM 750 k arrays and the results were analyzed according to biological information science database. The fetal development was regularly inspected. The follow-up were conducted with outcomes of pregnancy and fetal postnatal conditions. Results In 421 cases of ultrasonographic soft markers, there were 30 fetuses with pathogenic chromosome abnormalities, including 4.0% chromosome aneuploid and 3.1% pathogenic copy number variations. The detection rate of pathogenic chromosome abnormalities in multiple soft markers was 9.9%, and the detection rate of single soft markers was 6.2%. The difference was of statistic significance(P<0. 05). Different soft markers varied in the degree of association with fetal pathogenic chromosomal abnormalities. The detection rate of nuchal translucency or nuchal fold thickening, choroid plexus cysts, lateral cerebral ventriculomegaly, Nasal bone absence or hypoplasia11, echogenic bowel, short femur length and single umbilical artery were 21.4%(6/28), 5.8%(2/34), 5.5%(4/74), 1%(3/27), 8.7%(2/23), 5.7%(2/35) and 3.7%(1/27). Conclusion Multiple soft markers and ultrasonographic soft marker: nasal bone absence or hypoplasia, nuchal translucency or nuchal fold thickening, lateral cerebral ventriculomegaly correlate with marked increased risk for fetal pathogenic chromosomal abnormality. CMA can identify chromosomal microdeletion/microduplication unrecognizab1 e by conventional karyotyping analysis. The application of CMA could increase the detection rate of pathogenic CNVs in fetuses with soft markers, and effectively reduce the occurrence of birth defects.
Objective To explore the application value for fetuses with ultrasonographic soft markers by genome-wide high resolution chromosomal microarray analysis(CMA) and investigate the relationship between Chromosome abnormalities and ultrasonographic soft markers. Methods 421 pregnant women with ultrasonographic soft markers without obvious structural abnormalities at the First Affiliated Hospital of AFMU(Air Force Medical University) from January 2015 to March 2018 were involved in the present study. All pregnant women performed invasive prenatal diagnosis. Microarray testing was performed using Affymetrix CytoScanTM 750 k arrays and the results were analyzed according to biological information science database. The fetal development was regularly inspected. The follow-up were conducted with outcomes of pregnancy and fetal postnatal conditions. Results In 421 cases of ultrasonographic soft markers, there were 30 fetuses with pathogenic chromosome abnormalities, including 4.0% chromosome aneuploid and 3.1% pathogenic copy number variations. The detection rate of pathogenic chromosome abnormalities in multiple soft markers was 9.9%, and the detection rate of single soft markers was 6.2%. The difference was of statistic significance(P<0. 05). Different soft markers varied in the degree of association with fetal pathogenic chromosomal abnormalities. The detection rate of nuchal translucency or nuchal fold thickening, choroid plexus cysts, lateral cerebral ventriculomegaly, Nasal bone absence or hypoplasia11, echogenic bowel, short femur length and single umbilical artery were 21.4%(6/28), 5.8%(2/34), 5.5%(4/74), 1%(3/27), 8.7%(2/23), 5.7%(2/35) and 3.7%(1/27). Conclusion Multiple soft markers and ultrasonographic soft marker: nasal bone absence or hypoplasia, nuchal translucency or nuchal fold thickening, lateral cerebral ventriculomegaly correlate with marked increased risk for fetal pathogenic chromosomal abnormality. CMA can identify chromosomal microdeletion/microduplication unrecognizab1 e by conventional karyotyping analysis. The application of CMA could increase the detection rate of pathogenic CNVs in fetuses with soft markers, and effectively reduce the occurrence of birth defects.
引文
[1] 高健,郭文潮,李小玲,等.7529例高危孕妇的细胞遗传学分析[J].中国妇幼保健,2015,(31):5427-5429.
[2] 李凤英,王艳香.胎儿超声软指标的临床结局分析[J].世界最新医学信息文摘,2016,16(50):131.
[3] Ahman A,Axelsson O,Maras G,et al.Ultrasonographic fetal soft markers in a low-risk population:prevalence,association with trisomies and invasive tests[J].Acta Obstet Gynecol Scand,2014,93(4):367-373.doi:10.1111/aogs.12334
[4] Cooley LD,Lebo M,Li MM,et al.American College of Medical Genetics and Genomics technical standards and guidelines:microarray analysis for chromosome abnormalities in neoplastic disorders[J].Genet Med,2013,15(6):484-494.doi:10.1038/gim.2013.49
[5] Hanemaaijer NM,Sikkema-Raddatz B,van der Vries G,et al.Practical guidelines for interpreting copy number gains detected by high-resolution array in routine diagnostics[J].Eur J Hum Genet,2012,20(2):161-165.doi:10.1038/ejhg.2011.174
[6] 陈翠华,裘毓雯,常清贤,等.胎儿染色体异常与产前超声特征的相关性研究[J].南方医科大学学报,2011,31(2):347-349.
[7] Raniga S,Desai PD.Parikh H Ultrasonographic soft markers of aneuploidy in second trimester:are we lost[J].MedGenMed,2006,8(1):9.
[8] Zhu H,Lin S,Huang L,et al.Application of chromosomal microarray analysis in prenatal diagnosis of fetal growth restriction[J].Prenat Diagn,2016,36(7):686-692.doi:10.1002/pd.4844
[9] Schmid M,Stary S,Blaicher W,et al.Prenatal genetic diagnosis using microarray analysis in fetuses with congenital heart defects[J].Prenat Diagn,2012,32(4):376-382.doi:10.1002/pd.2862
[10] Sansovic I,Ivankov AM,Bobinec A,et al.Chromosomal microarray in clinical diagnosis:a study of 337 patients with congenital anomalies and developmental delays or intellectual disability[J].Croat Med J,2017,58(3):231-238.
[11] Li X,Liu Y,Yue S,et al.Uniparental disomy and prenatal phenotype:Two case reports and review[J].Medicine (Baltimore),2017,96(45):e8474.
[12] Kawashima S,Nakamura A,Inoue T,et al.Maternal Uniparental Disomy for Chromosome 20:Physical and Endocrinological Characteristics of Five Patients[J].J Clin Endocrinol Metab,2018,103(6):2083-2088.doi:10.1210/jc.2017-02780
[13] Kagami M,Nagasaki K,Kosaki R,et al.Temple syndrome:comprehensive molecular and clinical findings in 32 Japanese patients[J].Genet Med,2017,19(12):1356-1366.doi:10.1038/gim.2017.53
[14] Li Z,Fu F,Lei T,et al.Application of chromosome microarray analysis for the delineation of pathogenesis for fetal ventriculomegaly[J].Zhonghua Yi Xue Yi Chuan Xue Za Zhi,2017,34(4):576-582.doi:10.3760/cma.j.issn.1003-9406.2017.04.024
[15] Ren Y,You YQ,Zhou HH,et al.Clinical analysis of 21 cases with short fetal femur in the third trimester[J].Zhonghua Fu Chan Ke Za Zhi,2017,52(2):86-92.doi:10.3760/cma.j.issn.0529-567X.2017.02.004
[16] Chen J,Yang J,Zhao S,et al.Identification of a novel mutation in the FGFR3 gene in a Chinese family with Hypochondroplasia[J].Gene,2018,641:355-360.doi:10.1016/j.gene.2017.10.062
[17] 梁萍,庞丽红,张柳娟.胎儿脉络丛囊肿的产前诊断与临床评估[J].现代妇产科进展,2017,26(3):213-215.
[18] 马涛,杨晓,岳军,等.妊娠中晚期超声软指标与胎儿染色体异常及其围生结局[J].实用妇产科杂志,2017,33(2):110-113.
[19] 高嵩,施连东,胡妍.超声软指标在染色体异常产前筛查中的应用价值[J].中国妇幼保健,2017,32(2):417-419.
[20] Wapner RJ,Martin CL,Levy B,et al.Chromosomal microarray versus karyotyping for prenatal diagnosis[J].N Engl J Med,2012,367(23):2175-2184.doi:10.1056/NEJMoa1203382
[21] Levy B.Wapner R Prenatal diagnosis by chromosomal microarray analysis[J].Fertil Steril,2018,109(2):201-212.doi:10.1016/j.fertnstert.2018.01.005
[2] 李凤英,王艳香.胎儿超声软指标的临床结局分析[J].世界最新医学信息文摘,2016,16(50):131.
[3] Ahman A,Axelsson O,Maras G,et al.Ultrasonographic fetal soft markers in a low-risk population:prevalence,association with trisomies and invasive tests[J].Acta Obstet Gynecol Scand,2014,93(4):367-373.doi:10.1111/aogs.12334
[4] Cooley LD,Lebo M,Li MM,et al.American College of Medical Genetics and Genomics technical standards and guidelines:microarray analysis for chromosome abnormalities in neoplastic disorders[J].Genet Med,2013,15(6):484-494.doi:10.1038/gim.2013.49
[5] Hanemaaijer NM,Sikkema-Raddatz B,van der Vries G,et al.Practical guidelines for interpreting copy number gains detected by high-resolution array in routine diagnostics[J].Eur J Hum Genet,2012,20(2):161-165.doi:10.1038/ejhg.2011.174
[6] 陈翠华,裘毓雯,常清贤,等.胎儿染色体异常与产前超声特征的相关性研究[J].南方医科大学学报,2011,31(2):347-349.
[7] Raniga S,Desai PD.Parikh H Ultrasonographic soft markers of aneuploidy in second trimester:are we lost[J].MedGenMed,2006,8(1):9.
[8] Zhu H,Lin S,Huang L,et al.Application of chromosomal microarray analysis in prenatal diagnosis of fetal growth restriction[J].Prenat Diagn,2016,36(7):686-692.doi:10.1002/pd.4844
[9] Schmid M,Stary S,Blaicher W,et al.Prenatal genetic diagnosis using microarray analysis in fetuses with congenital heart defects[J].Prenat Diagn,2012,32(4):376-382.doi:10.1002/pd.2862
[10] Sansovic I,Ivankov AM,Bobinec A,et al.Chromosomal microarray in clinical diagnosis:a study of 337 patients with congenital anomalies and developmental delays or intellectual disability[J].Croat Med J,2017,58(3):231-238.
[11] Li X,Liu Y,Yue S,et al.Uniparental disomy and prenatal phenotype:Two case reports and review[J].Medicine (Baltimore),2017,96(45):e8474.
[12] Kawashima S,Nakamura A,Inoue T,et al.Maternal Uniparental Disomy for Chromosome 20:Physical and Endocrinological Characteristics of Five Patients[J].J Clin Endocrinol Metab,2018,103(6):2083-2088.doi:10.1210/jc.2017-02780
[13] Kagami M,Nagasaki K,Kosaki R,et al.Temple syndrome:comprehensive molecular and clinical findings in 32 Japanese patients[J].Genet Med,2017,19(12):1356-1366.doi:10.1038/gim.2017.53
[14] Li Z,Fu F,Lei T,et al.Application of chromosome microarray analysis for the delineation of pathogenesis for fetal ventriculomegaly[J].Zhonghua Yi Xue Yi Chuan Xue Za Zhi,2017,34(4):576-582.doi:10.3760/cma.j.issn.1003-9406.2017.04.024
[15] Ren Y,You YQ,Zhou HH,et al.Clinical analysis of 21 cases with short fetal femur in the third trimester[J].Zhonghua Fu Chan Ke Za Zhi,2017,52(2):86-92.doi:10.3760/cma.j.issn.0529-567X.2017.02.004
[16] Chen J,Yang J,Zhao S,et al.Identification of a novel mutation in the FGFR3 gene in a Chinese family with Hypochondroplasia[J].Gene,2018,641:355-360.doi:10.1016/j.gene.2017.10.062
[17] 梁萍,庞丽红,张柳娟.胎儿脉络丛囊肿的产前诊断与临床评估[J].现代妇产科进展,2017,26(3):213-215.
[18] 马涛,杨晓,岳军,等.妊娠中晚期超声软指标与胎儿染色体异常及其围生结局[J].实用妇产科杂志,2017,33(2):110-113.
[19] 高嵩,施连东,胡妍.超声软指标在染色体异常产前筛查中的应用价值[J].中国妇幼保健,2017,32(2):417-419.
[20] Wapner RJ,Martin CL,Levy B,et al.Chromosomal microarray versus karyotyping for prenatal diagnosis[J].N Engl J Med,2012,367(23):2175-2184.doi:10.1056/NEJMoa1203382
[21] Levy B.Wapner R Prenatal diagnosis by chromosomal microarray analysis[J].Fertil Steril,2018,109(2):201-212.doi:10.1016/j.fertnstert.2018.01.005
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |