产前诊断中常见染色体异常的快速检测与核型分析技术的应用

最常见的胎儿染色体异常多发生于21、18、13号常染色体和性染色体X、Y。染色体数目异常或拷贝数的改变，包括21三体（唐氏综合征）、18三体（Edwards综合征）、13三体（Patau综合征）、45，X（特纳综合征）、47，XXY（Klinefelter综合征）和三倍体，约占产前诊断中有临床意义的染色体异常的80％。唐氏综合征可发生神经系统发育迟缓，心脏和其他器官的先天畸形；     

超声在18-三体综合征产前诊断中的意义

目的 探讨超声在18-三体综合征产前诊断中的意义。方法 对我院1年来经羊水细胞或脐血细胞染色体核型分析确诊为18-三体综合征的5例胎儿超声影像资料进行回顾性分析，评估超声在产前对18-三体综合征胎儿检出的临床价值。结果 5例18-三体综合征患儿至少存在1种以上的超声异常声像。结论 妊娠期超声可检测到18-三体胎儿在形态结构上发生的异常，结合羊水或脐血染色体核型诊断，对于提高18-三体综合征胎儿的产前诊断率，降低严重染色体病缺陷患儿的出生率具有重要意义。     

产前诊断中常见染色体异常的快速诊断

最常见的胎儿染色体异常发生在21,18,13号常染色体和性染色体X、Y。染色体数目异常或拷贝数的改变,包括21-三体(唐氏综合征),18-三体(Edward综合征),13-三体(Patau综合征),45,X(特纳综合征),47,XXY(Klinefelter综合征)和三倍体,约占产前诊断中有临床意义的染色体异常的80%。对这些常见的染色体数目异常,标准的传统产前诊断方法是对羊膜腔穿刺获得的羊水细胞或绒毛抽吸获得的绒毛细胞进行培养,对染色体有丝分裂期的核分裂相进行分析。这就是大家所知的核型分析。除了常见的染色体数目异常,对所有的23对染色体都进行检查,可以检查出包括染…     

细菌人工染色体标记-微球鉴别/分离法在产前诊断中的临床应用价值

目的:探讨细菌人工染色体标记-微球鉴别/分离法(BoBs)在产前诊断中的临床应用价值。方法:对2015年1月至2018年4月空军军医大学第一附属医院4882例有产前诊断指征的孕妇羊水细胞行染色体核型分析和BoBs检测,检测结果进行比较分析。结果:4882例羊水中共检出胎儿染色体异常289例,异常检出率5.92%。其中染色体核型分析检出271例,BoBs检出266例。不同产前诊断指征下,无创产前检测高风险组的染色体异常检出率最高,占56.00%。289例异常核型中,染色体非整倍体239例,BoBs检测结果与染色体核型分析结果吻合;染色体微缺失/微重复综合征21例,染色体核型分析仅检出3例;性染色体嵌合11例,BoBs检出6例;染色体结构异常18例,BoBs均未检出。结论:BoBs技术是一种可靠的检测技术,可以全面快速检测胎儿染色体非整倍体及9种常见的微缺失/微重复综合征,与染色体核型分析联合可以提高产前诊断的效率及准确性,具有较高的临床应用价值。     

无创产前检测进行染色体缺失或重复检测的临床应用价值

目的:探讨无创产前检测(NIPT)进行染色体缺失或重复检测的临床应用价值。方法:对传统产前筛查异常、既往有唐氏儿分娩史及高龄孕妇等3500例孕妇采集外周血,采用Illumina测序技术检测母体血浆胎儿游离DNA(cff DNA),分析胎儿性染色体及除21、13、18号染色体以外的其他常染色体信息,对NIPT阳性的孕妇进行遗传咨询,对其中自愿进行介入性产前诊断的,行染色体核型分析及染色体微阵列分析(CMA)进行验证。结果:3500例接受NIPT的病例中,检出32例常染色体异常(除外21、13、18号),其中有11例接受介入性产前诊断,染色体核型分析及CMA检测分别提示3例异常,符合率27.3%(3/11)。检出45例性染色体异常,其中有23例接受介入性产前诊断,染色体核型分析及CMA检测分别确诊12例异常,符合率52.2%(12/45)。结论:NIPT在预测胎儿性染色体异常及常染色体(除外21、13、18号)异常方面有一定的参考价值,但需要进行染色体核型分析和(或)CMA检测进行验证。     

羊水细胞染色体核型分析和微列阵比较基因组杂交技术验证无创产前检测的临床意义

目的:探讨羊水细胞染色体核型分析技术和微列阵比较基因组杂交技术(array-CGH)验证无创产前检测(NIPT)的临床意义。方法:对NIPT提示信号异常的95例孕妇行羊膜腔穿刺术,抽取羊水进行培养后行染色体核型分析验证其符合率;同时对提示除外21-三体、18-三体、13-三体的常染色体异常(即其他常染色体异常)的患者行array-CGH分析,验证其符合率。结果:NIPT提示21-三体高风险的染色体核型分析符合率86.96%(40/46);18-三体的染色体核型分析符合率76.92%(10/13);13-三体染色体核型分析符合率0(0/2)。性染色体核型分析的符合率50.00%(9/18),其中1例性染色体异常的染色体核型分析为46,XX,del(Xq23-25),行array-CGH验证,提示为X染色体该区带11.9 M的片段缺失。其他常染色体异常的染色体核型分析符合率12.50%(2/16),其array-CGH验证的符合率25.00(4/16)。结论:NIPT的结果需要验证,经典的羊水细胞染色体核型分析技术可以验证胎儿染色体数目和结构异常,array-CGH可以验证微缺失或者微重复,分辨率更高。     

STR-PCR在产前诊断胎儿唐氏综合征中的应用

目的:研究通过多重荧光定量PCR诊断胎儿染色体非整倍体用于临床快速产前诊断的可行性。方法:从孕中期羊水中提取胎儿DNA,通过多重荧光定量PCR使用STR对13、18、21号染色体进行非整倍体筛查,筛查结果异常者再进行快速诊断。用PCR诊断的羊水标本同时使用"金标准"染色体核型分析法做对比。结果:34例羊水标本中2例标本由于母血污染严重未行PCR检测,1例标本经PCR及核型分析均失败,29例标本经PCR和核型分析诊断为正常染色体,2例标本经PCR和核型分析诊断为21-三体。结论:通过STR-PCR法使用多重荧光酶联聚合反应探针产前诊断胎儿唐氏综合征是临床快速产前诊断的有效方法之一。     

产前诊断胎儿ZTTK综合征1例

本文报道了1例产前诊断的ZTTK综合征胎儿。孕妇因配偶染色体平衡易位, 行胚胎植入前遗传学诊断。孕18周+取羊水细胞行染色体核型分析及基因组拷贝数变异测序均未发现异常。孕23周+5及孕26周+3超声检查显示严重胎儿生长受限、小脑发育异常、骶骨及尾骨显示欠清、脊柱裂, 孕23周+6胎儿颅脑MRI显示胎儿双侧小脑半球体积小, 大枕大池。对胎儿及其父母行全外显子组测序, 结果显示胎儿SON 基因3号外显子存在1个杂合变异c.2092delG(p.Glu698fs*4), 父母不存在该变异, 为新发变异;该位点为致病性, 关联疾病为ZTTK综合征。经遗传咨询, 孕妇及家属选择终止妊娠。     

无创DNA检测在诊断高龄孕妇胎儿非整倍体中的应用

目的:探讨高龄妊娠胎儿染色体异常的风险以及无创DNA产前检测(NIPT)在诊断高龄孕妇胎儿非整倍体染色体病中的应用价值。方法:选择≥35岁的高龄孕妇2714例,按年龄分为35~39岁,≥40岁两组,采用NIPT高通量测序检测孕妇血浆游离DNA,并对检测结果提示21-三体、18-三体、13-三体及性染色体高风险者行羊膜腔穿刺术及胎儿染色体核型分析,对检测结果阴性者通过电话随访进行验证。计算NIPT检测的敏感度、特异度、阳性预测值、阴性预测值及Youden指数。结果:2714例高龄孕妇NIPT检测结果提示胎儿非整倍体染色体异常高风险47例,6例高风险孕妇拒绝侵入性产前诊断,余41例高风险孕妇行羊膜腔穿刺术及羊水细胞染色体核型分析,结果显示21-三体19例,18-三体1例,13-三体2例,性染色体异常7例。与现有的金标准羊膜腔穿刺术核型分析相比较,NIPT对高龄孕妇除外性染色体异常的胎儿非整倍体染色体异常检出敏感度为100.00%,特异度为99.93%,阳性预测值为90.91%,阴性预测值为100.00%,Youden指数为0.99。进一步通过年龄分组发现,40岁及以上年龄组异常率显著高于35~39岁年龄组(P=0.011)。结论:高龄孕妇可通过NIPT快速、安全地筛查出胎儿非整倍体染色体异常,减少侵入性产前检测比例,降低胎儿出生缺陷率。     

6047例高龄孕妇胎儿染色体核型结果分析

目的:分析高龄孕妇中不同年龄阶段及其他高危因素孕妇发生胎儿染色体异常的特点,以探讨针对单一年龄因素高龄孕妇的产前筛查及诊断策略。方法:本研究收集近三年在首都医科大学附属北京妇产医院产前诊断中心进行产前诊断的高龄孕妇(预产期年龄≥35岁)的临床资料,共6047例,分为4组:A组预产期年龄≤40岁,无其他高危因素;B组预产期年龄≤40岁,存在其他高危因素;C组预产期年龄>40岁,无其他高危因素;D组预产期年龄>40岁,存在其他高危因素。针对胎儿染色体核型分析结果进行回顾性研究。结果:①胎儿染色体异常的总发生率为6.10%,其中非整倍体为4.10%[21三体综合征(T21)为2.30%,18三体综合征(T18)为0.79%,性染色体数目异常为0.94%,13三体综合征(T13)为0.07%],染色体结构异常为1.97%。②A组染色体非整倍体异常(包括T21、T18、性染色体数目异常)及染色体结构异常与B组比较差异均有统计学意义(P<0.01,P<0.05);A组与C组的T21、T18、性染色体数目异常比较,差异有统计学意义(P<0.01,P<0.05),两组染色体结构异常发生率比较差异无统计学意义(P>0.05);B组与D组的T21、T18、性染色体数目异常、染色体结构异常发生率差异无统计学意义(P>0.05);C组与D组的T18、性染色体数目异常、染色体结构异常发生率差异无统计学意义(P>0.05),两组间T21发生率差异有统计学意义(P<0.05)。③单纯高龄因素的孕妇与非单纯高龄因素的孕妇比较,胎儿染色体异常的发生率前者明显低于后者,其发生率随着年龄的增加而呈现逐渐交汇的趋势;而胎儿染色体结构异常的发生率比较,两组间差异无统计学意义。结论:当存在单独年龄因素时,预产期年龄≤40岁的孕妇,其发生胎儿非整倍体异常的风险显著低于预产期年龄>40岁的孕妇,也低于具有其他产前诊断高危因素的人群,采用恰当的产前筛查技术有助于提高此类人群的产前诊断效率。     

Prenatal diagnosis of Cri-du-Chat syndrome with concomitant distal trisomy 10q syndrome in one fetus with ultrasound anomalies

ObjectiveThe aim of this work was to characterize the genetic abnormalities and prenatal diagnosis indications in one fetus with Cri-du-Chat syndrome with codependent 10q24.2-q26.3 duplication in prenatal screening.Materials and methodsA 31-year-old woman had a second trimester serum screening that indicated the fetus was at low risk. During this pregnancy, the woman underwent amniocentesis at 18⁺⁴ weeks' gestation because of adverse fertility history and nuchal fold thickening. Cytogenetic analysis and next-generation sequencing analysis were simultaneously performed to provide genetic analysis of fetal amniotic fluid. According to abnormal results, parental chromosome karyotype of peripheral blood was performed to analysis.ResultsCNV-seq detected a 14.00 Mb deletion at 5p15.33-p15.2 and a 34.06 Mb duplication at 10q24.2-q26.3 in the fetus. Cytogenetic analysis of the fetus revealed a karyotype of 46, XY, der(5) t(5;10) (p15.2;q26.3). The karyotype of pregnant women was 46,XX,t(5;10) (p15.2;q24.2). The pregnancy was subsequently terminated after sufficient informed consent.ConclusionThis is the first study that reports prenatal diagnosis of a Cri-du-Chat syndrome with concomitant 10 q24.2-q26.3 duplication. Adverse pregnancy history has to be as an important indicator for prenatal diagnosis, and the genetic factors of abnormal pregnancy should be identified before next pregnancy. Nuchal fold thickening is closely related to fetal abnormalities. Combined with ultrasonography, the use of CNV-seq will improve the diagnosis of submicroscopic chromosomal aberrations in fetuses with congenital anomalies.     

Prenatal diagnosis and molecular cytogenetic analysis of partial monosomy 10q (10q25.3-->qter) and partial trisomy 18q (18q23-->qter) in a fetus associated with cystic hygroma and ambiguous genitalia

OBJECTIVES: To present the prenatal diagnosis and molecular cytogenetic analysis of a fetus with nuchal cystic hygroma and ambiguous genitalia. CASE AND METHODS: Amniocentesis was performed at 16 weeks' gestation because of the abnormal fetal sonographic finding of a large septated nuchal cystic hygroma. Genetic amniocentesis revealed a terminal deletion in the long arm of chromosome 10. The paternal karyotype was subsequently found to be 46,XY,t(10;18)(q25.3;q23). The maternal karyotype was normal. The pregnancy was terminated. A hydropic fetus was delivered with a septated nuchal cystic hygroma and ambiguous genitalia. Fluorescence in situ hybridization (FISH), microarray-based comparative genomic hybridization (CGH), and polymorphic DNA markers were used to investigate the involved chromosomal segments. RESULTS: FISH study showed absence of the 10q telomeric probe and presence of the 18q telomeric probe in the derivative chromosome 10. Microarray-based CGH analysis showed loss of distal 10q and gain of distal 18q. Polymorphic DNA marker analysis determined the breakpoints. The fetal karyotype was 46,XY,der(10)t(10;18)(q25.3;q23)pat. The chromosome aberration resulted in partial monosomy 10q (10q25.3-->qter) and partial trisomy 18q (18q23-->qter). CONCLUSIONS: The present case provides evidence that partial monosomy 10q (10q25.3-->qter) with partial trisomy 18q (18q23-->qter) can be a genetic cause of fetal cystic hygroma and ambiguous genitalia. Cytogenetic analysis for prenatally detected structural abnormalities may detect unexpected inherited chromosome aberrations.     

Prenatal diagnosis of a fetus affected with Down syndrome and deletion 1p36 syndrome by fluorescence in situ hybridization and spectral karyotyping

OBJECTIVE: A fetus having partial trisomy of the distal part of chromosome 21q due to a de novo translocation is reported here. METHOD: A 29-year-old woman received amniocentesis at 18 weeks of gestation because of abnormal ultrasound findings including bilateral choroid plexus cysts, atrioventricular septal defects, rocker-bottom feet, and possible hydrocephalus. RESULTS: Cytogenetic analysis revealed 46,XY, add(1)(p36.3), in which an additional material of unknown origin was attached to one of the terminal short arms of chromosome 1. Parental blood studies showed normal karyotypes in both parents. Spectral karyotyping was then performed and the origin of the additional material locating at chromosome 1p was found to be from chromosome 21. Conventional fluorescence in situ hybridization analysis was also used and confirmed the spectral karyotyping findings by use of a chromosome 21 specific painting probe, a locus specific probe localized within bands 21q22.13-q22.2 and a 21q subtelomeric probe. A hidden Down syndrome caused by a de novo translocation in this fetus was therefore diagnosed and the karyotype was designated as 46,XY, der(1)t(1;21)(p36.3;q22.1).ish der(1)(WCP21+, LSI 21+, 1pTEL-, 21q TEL+) de novo. Clinical features of the 1p36 deletion syndrome are also reviewed and may contribute to some features of this fetus. Termination of pregnancy was performed at 20 weeks of gestation. CONCLUSION: To our knowledge, our case appears to be the first to have partial monosomy 1p and partial trisomy 21q caused by de novo translocation being diagnosed prenatally.     

Perinatal cytogenetic discrepancy in a fetus with low-level mosaicism for trisomy 21 and a favorable outcome

ObjectiveWe present perinatal cytogenetic discrepancy in a fetus with low-level mosaicism for trisomy 21 and a favorable outcome.Case reportA 40-year-old woman underwent amniocentesis at 19 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 47,XY,+21[7]/46,XY[14]. She underwent cordocentesis 21 weeks of gestation, and the karyotype of cord blood was 47,XY,+21[13]/46,XY[38]. The prenatal ultrasound findings were unremarkable. After genetic counseling of a favorable outcome of low-level mosaic trisomy 21 at amniocentesis, the parents decided to continue the pregnancy, and a 3128-g phenotypically normal male baby was delivered at 38 weeks of gestation without phenotypic features of Down syndrome. Postnatal cytogenetic analysis of cord blood revealed a karyotype of 47,XY,+21[3]/46,XY[47]. The placenta had a karyotype of 47,XY,+21[8]/46,XY[32], and the umbilical cord had a karyotype of 47,XY,+21[5]/46,XY[35]. Array comparative genomic hybridization analysis on the DNA extracted from cord blood revealed no genomic imbalance. Polymorphic DNA marker analysis excluded uniparental disomy 21. Interphase fluorescence in situ hybridization analysis on urinary cells revealed trisomy 21 signals in 2/102 (1.96%) cells compared with 2/103 (1.94%) cells in normal control.ConclusionThe cells of abnormal cell line in prenatally detected mosaic trisomy 21 may decrease in number or disappear in various tissues as the fetus grows, and there exists perinatal cytogenetic discrepancy in mosaic trisomy 21 detected at prenatal diagnosis.     

Prenatal diagnosis of recurrent mosaic ring chromosome 13 of maternal origin

ObjectiveWe present prenatal diagnosis of recurrent mosaic ring chromosome 13 [r(13)] of maternal origin.Case ReportA 27-year-old woman underwent amniocentesis at 17 weeks of gestation because of a past history of fetal abnormality caused by mosaic r(13) in the previous fetus associated with fetal intrauterine growth restriction (IUGR), a karyotype of 46,XY,r(13)[23]/45,XY,-13[10]/46,XY,idic r(13)[2] and a maternal origin of abnormal r(13). The parental karyotypes were normal. During this pregnancy, amniocentesis revealed a karyotype of 46,XX,r(13)[12]/45,XX,-13[8] and a 22.80-Mb deletion of chromosome 13q31.3-q34. The pregnancy was subsequently terminated, and a malformed fetus was delivered with craniofacial dysmorphism. Repeat amniocentesis revealed a karyotype of 46,XX,r(13)(p11.1q31)[18]/45,XX,-13[12]. The placenta had a karyotype of 46,XX,r(13)(p11.1q31)[27]/45,XY,-13[13]. Polymorphic DNA marker analysis using the DNA derived from the parental bloods and umbilical cord confirmed a maternal origin of the abnormal r(13).ConclusionPrenatal diagnosis of mosaic r(13) in consecutive pregnancies should raise a suspicion of parental gonadal mosaicism, and polymorphic DNA marker analysis is useful for determination of the parental origin of recurrent aneuploidy under such a circumstance.     

Prenatal diagnosis of trisomy 18 as true mosaicism by three-dimensional ultrasonography: a case report

Trisomy of chromosome 18 is the second most common autosomal trisomy, occurring in approximately 1:7,000 live births. Its prenatal diagnosis through abnormal findings in ultrasound with later analysis of fetal karyotype is important for a definition of the prognosis and counseling of the patients. We describe a case of trisomy 18 as true mosaicism diagnosed through amniocentesis in the second trimester of pregnancy, associated to the presence of multiple fetal phenotypic alterations. We focus on the importance of fetal morphological study through three-dimensional ultrasonography, which was highly important for clearly showing the fetus’ structural alterations, helping parents to understand better the pathology and allowing them to reason about the continuity of the gestation.     

Monozygotic twins with trisomy 18 of paternal origin: prenatal diagnosis and molecular cytogenetic characterization in a pregnancy with one structurally abnormal living fetus and one intrauterine fetal demise

ObjectiveTo present prenatal diagnosis and molecular cytogenetic characterization of trisomy 18 in a monozygotic twin pregnancy, with one structurally abnormal living fetus and one intrauterine fetal demise.Case ReportA 38-year-old woman was referred for amniocentesis at 16 weeks of gestation because of advanced maternal age. Prenatal ultrasound revealed a monozygotic twin pregnancy, with one structurally abnormal living fetus, and one fetal demise. The body structure details of the dead fetus could not be identified, whereas holoprosencephaly and omphalocele were identified in the living fetus on prenatal ultrasound. Quantitative fluorescent polymerase chain reaction assays using polymorphic DNA markers specific for chromosome 21 and chromosome 18, were applied to the uncultured amniocytes in the amniotic cavity of the living fetus and the cultured amniocytes in the amniotic cavity of the fetus with intrauterine fetal demise. The specimen showed a dosage ratio of 2:1 (paternal:maternal) for chromosome 18-specific markers in both twins. The result was consistent with monozygosity and trisomy 18, and the trisomy 18 was possibly caused by a paternal second meiotic division non-disjunction error or a postzygotic mitotic error. Conventional cytogenetic analysis revealed a karyotype of 47,XY,+18 in both twins. The pregnancy was terminated at 19 weeks of gestation, and a 2 g small-for-date macerated twin A and a 166 g malformed twin B were delivered. Twin A manifested cebocephaly and omphalocele, and twin B manifested premaxillary agenesis and omphalocele.ConclusionThe present case provides evidence that fetal wastage may occur in one of the co-twins in monozygotic twins associated with trisomy 18, and this may in part explain the very rare occurrence of living monozygotic twins with trisomy 18.     

Prenatally diagnosed microdeletion in the TCOF1 gene in fetal congenital primary Treacher Collins Syndrome

ObjectiveTo study prenatal diagnosis of congenital Treacher Collins syndrome, an etiology of craniofacial abnormalities.Case reportWe present a case of fetal craniofacial abnormalities identified by antepartum sonography screening in the third trimester (28 weeks); features of micrognathia, hypoplastic zygomatic arches and bilateral low-set microtia were detected. Due to the unknown severity of the craniofacial abnormalities and poor prognosis, the parents decided to terminate the fetus after through counselling. A normal female karyotype was detected. The parents consented to chromosome microarray analysis (CMA), which identified a de novo mutation of the TCS1 gene locus on chromosome 5.ConclusionMolecular CMA is an effective tool for prenatal diagnosis of congenital craniofacial abnormalities associated with Treacher Collins syndrome.     

Prenatal diagnosis of the Dandy-Walker malformation and ventriculomegaly associated with partial trisomy 9p and distal 12p deletion

OBJECTIVES: To present the prenatal diagnosis and perinatal findings of partial trisomy 9p and distal 12p deletion. METHODS AND RESULTS: Amniocentesis was performed at 17 gestational weeks due to a balanced reciprocal translocation t(9;12)(p11.2;p13.3) in the mother. The father's karyotype was normal. The family had a 5-year-old daughter with a Dandy-Walker malformation and a trisomy 9p syndrome. Cytogenetic analysis of the cultured amniotic fluid cells revealed a 46,XY,der(12)t(9;12)(p11.2;p13.3)mat karyotype with partial monosomy 12p(12pter-->p13.3) and partial trisomy 9p(9pter-->p11.2). Sonographic examination of the fetal brain and skull showed bilateral ventriculomegaly, brachycephaly and a Dandy-Walker malformation with an enlarged cisterna magna and absence of the cerebellar vermis. The pregnancy was terminated subsequently. At autopsy, the proband manifested agenesis of the cerebellar vermis and a typical trisomy 9p phenotype. CONCLUSION: Fetuses with partial trisomy 9p(9pter-->p11.2) may present a Dandy-Walker malformation and ventriculomegaly on prenatal ultrasound in the second trimester. A dosage effect of genes located on 9pter-->p11.2 may be associated with the abnormal development of the central nervous system in patients with partial or complete trisomy 9.     

46,XY,18q+/46,XY,18q- mosaicism in a fragile X prenatal diagnosis

OBJECTIVES: We describe a fetus with confined placental mosaicism for 46,XY,dup(18)(q21q23)/46,XY, del(18)(q21) in which finally the 18q- cell line formed the embryo. This prenatal diagnosis was performed on a pregnant woman carrying a premutation in the FMR1 gene. The purpose of the current study was to characterise the final fetus genotype and to discuss how this chromosomal abnormality was originated. METHODS: Conventional cytogenetic analyses were performed from chorionic villi, amniocytes, and fetal blood samples in order to establish the fetal chromosome constitution. Molecular studies with microsatellite markers and CGH were carried out to this end. PCR and Southern blot were used to analyse the CGG-repeat region of the FMR1 gene. RESULTS: An initial chorionic villi sample analysis showed a normal allele for the fragile X syndrome, but an abnormal 46,XY,dup(18)(q21q23) karyotype. Amniocentesis was subsequently performed, and a different 46,XY,del(18)(q21) cell line was detected. Re-examination of original chorionic villi sample evidenced a mosaicism for 46,XY,dup(18)(q21q23)/46,XY,del(18)(q21). Molecular findings allowed us to determine that the deletion expands at least 20 Mb and that it is paternally inherited. CONCLUSION: Two different cell lines with structural abnormalities on chromosome 18 were formed as a consequence of an unequal sister chromatid exchange during the first post-zygotic division. This case reinforces the necessity of performing a karyotype in all prenatal diagnosis even when the indication is for a monogenic disease.