羊水间期细胞荧光原位杂交检测残余风险评估:6125例产前细胞遗传学诊断回顾性分析

Evaluation of residual risk of cytogenetic abnormalities after prenatal diagnosis by interphase fluorescence in situ hybridization in second-trimester:a retrospective analysis of conventional karyotyping on 6125 consecutive amniotic fluid specimens

目的评估中孕期羊水间期细胞荧光原位杂交(FISH)检测之后漏诊非13、18、21、X、Y染色体的非整倍体异常核型的残余风险,从产前咨询的角度来评价间期FISH检测在产前诊断中的作用。方法对6 125例中孕期羊水传统核型分析的结果进行回顾性分析,假设这些病例均进行间期FISH检测,计算在三大产前诊断指征(孕妇高龄、孕母血清学筛查18-三体或21-三体高风险、妊娠23周前超声发现胎儿有结构异常)情况下间期FISH检测的检出率以及残余风险。结果从2011年1月至2014年9月共有6 125例单胎孕妇行中孕期羊水细胞核型分析,共检出207例(3.38%)异常核型。有161例(77.8%)为涉及13、18、21、X、Y染色体非整倍体的异常核型(包括嵌合体),其间期FISH检测结果为阳性。有46例(22.2%)异常结果是非13、18、21、X、Y染色体的非整倍体,其中包括平衡性结构重排31例(67.4%)、非平衡性结构重排14例(30.4%)、其他染色体非整倍体1例(2.2%)。在这46例异常核型中,有6例涉及21号染色体和1例涉及13号染色体的不平衡性重排的间期FISH检测结果为阳性,其余39例间期FISH检测结果均为阴性。计算间期FISH检测的检出率为81.2%(168/207),间期FISH检测的残余风险为0.65%(39/5957)。结论间期FISH检测是核型分析的有效补充,但不能取代核型,单纯行间期FISH检测进行产前诊断会漏诊约18.8%的染色体异常。在产前遗传咨询时应向病人解释间期FISH的检出率和残余风险,了解间期FISH的优点和局限性,帮助其选择合适的产前诊断手段。

Objective： To analyze the results from conventional cytogenetic studies of second-trimester amniocytes and determine the residual risk for a cytogenetic abnormality if interphase fluorescence in situ hybridization（FISH）,capable of only detecting aneuploidies for chromosome 13,18,21,X,Y was performed and did not reveal an abnormality.Methods：Results from conventional karyotyping on 6 125 consecutive amniotic fluid specimens were analyzed retrospectively.Detection rate and residual risk of interphase FISH were calculated for the three major clinical indications for prenatal diagnosis（advanced maternal age,abnormal maternal serum screening indicating increased risks for trisomy 18 or trisomy 21,ultrasound abnormality）.Results： A total of 6 125 consecutive karyotyping on second-trimester amniocytes for prenataldiagnosis were performed from January 2011 to Spetember 2014.Two hundreds and seven（3.38%）cases of abnormal karyotypes were found,including 161 cases of aneuploidies involving chromosome 13,18,21,X and Y,which were considered detectable by interphase FISH.Forty six cases of chromosomal anomalies other than the aneuploidies of chromosome 13,18,21,X and Y were diagnosed after karyotyping and not detected by interphase FISH,including 31 cases of balanced rearrangements,14 cases of imbalanced rearrangenents,1case of pseudomosaic of trisomy 20.Among the 46 cases of chromosomal anomalies,6cases of imbalanced rearrangements involving chromosome 21 and 1case of imbalanced rearrangement involving chromosome 13 showed positive FISH results,and the other 39 cases showed negative FISH results,with a total detection rate of interphase FISH of 81.2%（168/207）and a residual risk of 0.65%（39/5957）following the interpahse FISH on second-trimester amniocytes.Conclusions：Interphase FISH is a useful adjunct to conventional karyotyping,but should not be considered as a replacement for karyotyping as too many structural chromosomal abnormalities will be missed.Providing patients with detection rate and residual risk during counselling could help them understand the advantages and limitations of interphase FISH in their prenatal diagnostic evaluation.