51例胎儿颈项透明层增厚的染色体核型及CNV-Seq结果分析
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摘要
目的对于胎儿NT≥3.0mm的孕妇通过绒毛或羊水取材术行染色体核型G显带分析同时行CNV-Seq技术检测,通过CNV-Seq技术在全基因组范围内检测染色体拷贝数变异(CNV),得到异常的CNV后,对其进行基因型与表型关系分析,以指导产前遗传咨询。方法选取2017年1月至6月在柳州市妇幼保健院产前诊断中心的48例孕11～13+6w超声诊断NT≥3.0mm孕妇,其中双胎孕妇2例(均为双绒双羊双胎,其中1例双胎一胎水囊瘤、死胎;另1例双胎两胎儿生长发育不一致),三胎孕妇1例(双绒叁羊叁胎),通过产前诊断取得胎儿样本51份(绒毛21份,羊水30份),同时对胎儿样本进行染色体核型G显带分析和CNV-Seq技术检测染色体拷贝数变异(CNV)。结果 51份胎儿样本均获得染色体核型G显带和CNV-Seq技术检测结果。CNV-Seq技术检测结果异常22例,检出率为43.14%,其中致病性CNV异常19例(86.36%),检出率为37.25%,非致病性CNV异常3例(13.64%),检出率为5.88%。致病性CNV异常中非整倍异常15例(78.95%),检出率为29.41%,与染色体核型G显带结果一致;染色体大片的缺失1例(5.26%),检出率为1.96%,染色体核型G显带结果46,XN,del(10)(q26);染色体微缺失、微重复3例(15.79%),检出率5.88%,染色体核型G显带结果未见异常,即在胎儿染色体核型G显带结果正常的34例病例中检出3例致病性微缺失、微重复(8.82%,3/34)。结论通过CNV-Seq技术检测,我们额外增加了8.82%NT增厚的胎儿异常检出率。对产前遗传咨询起着重要作用,也给产前遗传咨询和疾病诊断提供可靠的依据和技术手段。
引文
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[2]Nieolaides KH.Azar G,Byrne D,et a1.Fetal nuchal translucency:ultrasound screening for chromosomal defects in first trimester of pregnancy[J].BMJ,1992,304(6831):867-869.
[3]ipale P,Hiilesmaa V,Salonen R,et al.Increased nuchal translucency as a marker for fetal chromosomal defects[J].N Engl JMed,1997,337(23):1654-1658.
[4]ijders RJ,Noble P,Sebire N,et a1.UK muhicentre project on assessment of risk of trisomy 21 by maternal age and fetal nuchal translucency thickness at 10-14weeks of gestation[J].Lancet,1998,352(9125):343-346.
[5]hitty LS,Kagan KO,Molina FS,et a1.Fetal nuchal translucency scan and early prenatal diagnosis of chromosomal abnormalities by rapid aneuploidy screening:observational study[J].BMJ,2006,332(7539):452-455.
[6]afner E,Schuchter K,Liebhart E,et a1.Results of routine fetal nuchal translucency measurement at weeks 10-13 in 423unselected pregnant women[J].Prenat Diagn,1998,18(1):29-34.
[7]ouka AP,Snijders RJ,Novakov A,et a1.Defects and syndromes in chromosomally normal fetuses with increased nuchal translucency thickness at 10-14 weeks of gestation[J].Ultrasound Obstet Gynecol,1998,11(6):391-400.
[8]mercati A,Panzarino M,Totaro I et a1.Increased nuchal translucency and short femur length as possible early signs of osteogenesis imperfecta type fll[J1.J Prenat Med,2013,7(1):5-8.
[9]Bestwick JP.Distribution of nuchal translucency in antenatal screen-ing for Down′s syndrome[J].Med Screen,2010,17(1):8.
[10]周祎,鲁云涯等.颈项透明层增厚胎儿的产前诊断及预后分析[J].中山大学学报(医学科学版),2013,11(6):888-893.
[11]杨鑫,符芳等.染色体微阵列分析在核型正常的颈项透明层增厚胎儿中的应用[J].中华医学遗传学杂志,2015,3.
[12]Splitt,MP;Hellens,S;Jones,et al.Deletion and Duplication of the same two BAC clones at 16p13.11 in two patients with distinctive phenotypes[M].British Human Genetics Conference,2007.
[13]El-Gbhary YM,Surti U,McPherson E,et al.Case of 22q13.3deletion as a result of asymmetrically dicentric 22.52nd Annual Meeting of the American-Society-of-Human-Genetics,2002.
[14]Kuuse,K;Tammur,P;Zordania,R;Ounap,K,Subtelomeric monosomy 6p and trisomy 22q13.3 in a dysmorphic and mentally retarded boy[M].6th,European Cytogenetics Conference,2007.
[15]Genevieve D,Sach P,Borie C,Dupuy O,Raoul M,Jacquemont ML,Sznajer Y,Pignal C,Thaly A,Vitu M,Baumann C,Evraud P,Verloes A,Eydoux P.Excess of the short arm of chromosome22 resulting in a duplication 22q13.3 in a girl with severe growth retardation:a possible pitfall in cytogenetics[M].52nd,Annual Meeting of the American-Society-of-Human-Genetics,2002.
[16]Aluigi M,Mancini M,Leo E,Castagnetti F,Baldazzi C,Barbieri E,Santucci MA.C22orf2 Gene(22q13.3)Translocation Downstream of Bcr Breakpoint(22q11)to the Derivative 9Chromosome Is Associated with Reduced Expression of Its Protein,the Beta-Catenin Antagonist Chibby,in Chronic Myeloid Leukemia Progenitors,.53rd Annual Meeting and Exposition of the American-Society-of-Hematology(ASH)/Symposium on the Basic Science of Hemostasis and Thrombosis,2011.
[17]Trembath,RC;Bonaglia,MC;Hennekam,RCM;Aldred,MA.AHO-like deletion syndrome:significant refinement of the minimal deleted region at 2q37.3.Annual Meeting of the American-Society-of-Human-Genetics,2003.
[18]Hoo J,Shrimpton AE,Braddock BR,Thomson LL,Stein CK.Deletion of GPR35 gene on 2q37.3 may account for Albright hereditary osteodystrophy like phenotype:Defining further genetic variants within and around GPR35 gene,2003.
[19]Soemedi R,et al.Contribution of Global Rare Copy-Number Variants to the Risk of Sporadic Congenital Heart Disease[J].The American Journal of Human Genetics,2012,91(3):489-501.16.
[20]Lalani SR,et al.Rare DNA copy number variants in cardiovascular malformations with extracardiac abnormalities[J].European Journal of Human Genetics.2012;21(2):173-81.