CAJ | 학술논문

目的评估妊娠中期羊水间期细胞荧光原位杂交(fluorescence in situ hybridization,FISH)检测后漏诊非13、18、21、X或Y染色体非整倍体异常核型的残余风险. 方法对中国医学科学院北京协和医学院北京协和医院2010年1月1日至2013年7月31日2 837例妊娠中期行羊膜腔穿刺术同时行间期细胞FISH检测和传统核型分析的病例及其结果进行回顾性分析.采用GLP 13/GLP21/CSP 18/CSPX/CSPY探针针对13、18、21、X或Y染色体进行间期细胞FISH检测.计算具有三大产前诊断指征(孕妇高龄、母体血清学筛查18或21-三体高风险、妊娠23周前超声发现胎儿有结构异常)的孕妇间期细胞FISH检测的检出率以及残余风险. 结果 2 837例标本中,共85例(3.0％)羊水细胞染色体核型分析异常.85例中的73例为13、18、21、X或Y染色体非整倍体的异常核型,间期细胞FISH结果均为阳性,其中21-三体共43例(包括2例嵌合体)、18-三体1 5例、13-三体l例、性染色体非整倍体14例(包括4例嵌合体).12例(14.1％)异常结果为非13、1 8、21、X或Y染色体的非整倍体,包括平衡性结构重排6例、非平衡性结构重排5例、其他染色体非整倍体1例.这12例中,间期细胞FISH结果阳性3例,均涉及21号染色体的不平衡性结构异常;阴性9例,其中4例遗传性平衡性重排和2例新生平衡性重排.2 837例病例间期细胞FISH分析对染色体异常的检出率为89.4％(76/85),异常核型漏诊率为14.1％(12/85),残余风险为0.43％(12/2 761). 结论间期细胞FISH检测是核型分析的有效补充,但不能取代核型分析,单纯间期细胞FISH检测进行产前诊断可能漏诊部分染色体结构异常.在产前遗传咨询时,应向患者解释间期细胞FISH的检出率和残余风险,合理选择产前诊断方法.
목적 평고임신중기양수간기세포형광원위잡교(fluorescence in situ hybridization,FISH)검측후루진비13、18、21、X혹Y염색체비정배체이상핵형적잔여풍험. 방법 대중국의학과학원북경협화의학원북경협화의원2010년1월1일지2013년7월31일2 837례임신중기행양막강천자술동시행간기세포FISH검측화전통핵형분석적병례급기결과진행회고성분석.채용GLP 13/GLP21/CSP 18/CSPX/CSPY탐침침대13、18、21、X혹Y염색체진행간기세포FISH검측.계산구유삼대산전진단지정(잉부고령、모체혈청학사사18혹21-삼체고풍험、임신23주전초성발현태인유결구이상)적잉부간기세포FISH검측적검출솔이급잔여풍험. 결과 2 837례표본중,공85례(3.0％)양수세포염색체핵형분석이상.85례중적73례위13、18、21、X혹Y염색체비정배체적이상핵형,간기세포FISH결과균위양성,기중21-삼체공43례(포괄2례감합체)、18-삼체1 5례、13-삼체l례、성염색체비정배체14례(포괄4례감합체).12례(14.1％)이상결과위비13、1 8、21、X혹Y염색체적비정배체,포괄평형성결구중배6례、비평형성결구중배5례、기타염색체비정배체1례.저12례중,간기세포FISH결과양성3례,균섭급21호염색체적불평형성결구이상;음성9례,기중4례유전성평형성중배화2례신생평형성중배.2 837례병례간기세포FISH분석대염색체이상적검출솔위89.4％(76/85),이상핵형루진솔위14.1％(12/85),잔여풍험위0.43％(12/2 761). 결론 간기세포FISH검측시핵형분석적유효보충,단불능취대핵형분석,단순간기세포FISH검측진행산전진단가능루진부분염색체결구이상.재산전유전자순시,응향환자해석간기세포FISH적검출솔화잔여풍험,합리선택산전진단방법.
Objective To evaluate the residual risk (i.e.failure risk in detecting aneuploidies abnormalities except for chromosome 13,18,21,X and Y) of cytogenetic abnormalities using interphase fluorescence in situ hybridization (FISH) for the second-trimester amniocytes.Methods The results of interphase FISH and conventional karyotyping of 2 837 consecutive amniotic fluid specimens were analyzed retrospectively.Probes for chromosomes 13,18,21,X and Y were used.The detection rate and residual risk for interphase FISH were calculated for the following three major clinical indications for prenatal diagnosis (advanced maternal age,abnormal maternal serum screening indicating an increased risk for trisomy 18 or trisomy 21,and ultrasound abnormalities).Results Consecutive interphase FISH and karyotyping of second-trimester amniocytes for prenatal diagnosis were performed from January 1,2010 to July 31,2013.Among the 2 837 cases,85 (3.0％) cases with abnormal karyotypes were found,including 73 cases of aneuploidies involving chromosome 13,18,21,X and Y,which were considered detectable by interphase FISH; 12 cases of chromosomal anomalies,other than aneuploidies of chromosome 13,18,21,X and Y,were diagnosed after karyotyping and were not detected by interphase FISH,including six cases of balanced rearrangements,five cases of imbalanced rearrangements,and one case of pseudomosaic of trisomy 20.Of these 12 chromosomal anomalies,three cases of imbalanced rearrangements involving chromosome 21 showed positive FISH results,and the other nine cases showed negative FISH results among which four case of hereditary balanced rearrangemerts and two cases of novel balanced rearrangements.The total detection rate for interphase FISH was 89.4％ (76/85),the misdiagnosis rate of chromosome abnormalities was 14.1％(12/85),and the residual risk was 0.43％ (12/2 761) following interphase FISH of the second-trimester amniocytes.Conclusions Interphase FISH is a useful adjunct to conventional karyotyping,but should not be regarded as a replacement for karyotyping as too many structural chromosomal abnormalities will be missed.Providing patients with a detection rate and residual risk during counselling may help them understand the advantages and limitations of interphase FISH in their prenatal diagnostic evaluation.