Prenatal diagnosis of maternal uniparental disomy 21 in association with low-level mosaic trisomy 21 at amniocentesis in a pregnancy associated with intrauterine growth restriction and a favorable outcome

ObjectiveWe present prenatal diagnosis of maternal uniparental disomy (UPD) 21 in association with low-level mosaic trisomy 21 at amniocentesis in a pregnancy associated with intrauterine growth restriction (IUGR) and a favorable outcome.Case reportA 42-year-old, gravida 2, para 0, woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis initially revealed a karyotype of 46,XX in 20/20 colonies of cultured amniocytes. Simultaneous array comparative genomic hybridization (aCGH) analysis on uncultured amniocytes revealed a result of arr [GRCh37] (21) × 3 [0.16], (X) × 2, compatible with mosaic trisomy 21. After extensive investigation, the final result of conventional cytogenetic analysis of cultured amniocytes was 47,XX,+21[1]/46,XX[40]. The parental karyotypes were normal. Repeat amniocentesis was performed at 21 weeks of gestation. The cultured amniocytes had a karyotype of 47,XX,+21[3]/46,XX[27] and the uncultured amniocytes had a mosaic trisomy 21 level of 8.8% (10/114 cells) by interphase fluorescence in situ hybridization (FISH), a mosaic trisomy 21 level of 10% (log₂ ratio = 0.08) by aCGH, and maternal UPD 21 by polymorphic DNA marker analysis. Prenatal ultrasound revealed IUGR. At 38 weeks of gestation, a phenotypically normal 2695-g baby was delivered. The cord blood and umbilical cord had the karyotype of 46,XX and maternal UPD 21. The placenta had a karyotype of 47,XX,+21[8]/46,XX[32] and a maternal origin of trisomy 21. Postnatal FISH analysis on 101 buccal mucosal cells showed 6.9% (7/101 cells) mosaicism compared with 2% (2/100 cells) in the normal control. The baby was doing well at age four months.ConclusionPregnancy with low-level mosaic trisomy 21 and maternal UPD 21 at amniocentesis can be associated with IUGR and a favorable outcome. Fetuses with maternal UPD 21 can be associated with mosaic trisomy 21 at amniocentesis.     

Prenatal diagnosis of mosaic trisomy 18 and maternal uniparental disomy 18 by amniocentesis in a pregnancy associated with cytogenetic discrepancy in various tissues and a favorable fetal outcome

ObjectiveWe present prenatal diagnosis of mosaic trisomy 18 and maternal uniparental disomy (UPD) 18 in a pregnancy with a favorable fetal outcome.Case reportA 34-year-old woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age, and the result was 47,XY,+18 [4]/46,XY [25] in cultured amniocytes. Simultaneous array comparative genomic hybridization (aCGH) on uncultured amniocytes revealed 65% mosaicism for trisomy 18. Prenatal ultrasound was normal. She consulted our hospital and underwent repeat amniocentesis at 22 weeks of gestation, and the result revealed a karyotype of 47,XY,+18 [9]/46,XY [12] in cultured amniocytes. Simultaneous aCGH on uncultured amniocytes revealed arr 18p11.32q23 × 2.4 (log₂ ratio = 0.3) consistent with 40% mosaicism for trisomy 18. Parental karyotypes were normal. Quantitative fluorescent polymerase chain reaction (QF-PCR) analysis on the DNA extracted from parental bloods and uncultured amniocytes confirmed maternal uniparental heterodisomy of chromosome 18. At 26 weeks of gestation, she underwent the third amniocentesis which revealed a karyotype of 47,XY,+18 [7]/46,XY [19] in cultured amniocytes. Simultaneous aCGH on uncultured amniocytes revealed arr 18p11.32q23 × 2.4 (log₂ ratio = 0.27) consistent with 40% mosaicism for trisomy 18. Interphase fluorescence in situ hybridization (FISH) on uncultured amniocytes revealed 38% (38/100 cells) mosaicism for trisomy 18. The woman was advised to continue the pregnancy, and a 2620-g phenotypically normal male baby was delivered at 40 weeks of gestation. At birth, the karyotypes of cord blood, umbilical cord and placenta were 47,XY,+18 [14]/46,XY [26], 47,XY,+18 [9]/46,XY [31] and 47,XY,+18 (40/40 cells), respectively. When follow-up at age 2½ months, the neonate was phenotypically normal. The peripheral blood had a karyotype of 47,XY,+18 [28]/46,XY [12], and interphase FISH analysis on buccal mucosal cells detected 6.4% (7/93 cells) mosaicism for trisomy 18, compared with 0% (0/100 cells) in the normal control. When follow-up at age seven months, the neonate was normal in development, and the peripheral blood had a karyotype of 47,XY,+18 [18]/46,XY [22].ConclusionsMosaic trisomy 18 at amniocentesis can be associated with cytogenetic discrepancy in various tissues, UPD 18 and a favorable fetal outcome. Prenatal diagnosis of mosaic trisomy 18 should alert the possibility of UPD 18 and include UPD testing.     

Prenatal diagnosis of maternal uniparental disomy 5 by amniocentesis associated with confined placental mosaicism for trisomy 5 and fetal trisomy 21 in a pregnancy

ObjectiveWe present prenatal diagnosis of maternal uniparental disomy (UPD) 5 by amniocentesis associated with confined placental mosaicism (CPM) for trisomy 5 and fetal trisomy 21 in a pregnancy.Case reportA 45-year-old woman underwent chorionic villus sampling (CVS) at 11 weeks of gestation because of maternal advanced age and an increased nuchal translucency of 4.0 mm in the first-trimester screening. CVS revealed a karyotype of 47,XY,+21[98]/48,XY,+5,+21[25]. Array comparative genomic hybridization (aCGH) analysis on the DNA extracted from chorionic villi revealed arr (5) × 3, arr (21) × 3 compatible with double trisomy 5 and trisomy 21. The woman underwent amniocenteses at 20 weeks and 22 weeks of gestation. Amniocenteses revealed a karyotype of 47,XY,+21. The parental karyotypes were normal. Quantitative fluorescent polymerase chain reaction (QF-PCR) on the DNA extracted from uncultured amniocytes showed trisomy 21 of maternal origin and maternal UPD 5. aCGH and interphase fluorescence in situ hybridization (FISH) on uncultured amniocytes confirmed trisomy 21. Prenatal ultrasound findings were unremarkable. The parents decided to continue the pregnancy, and a 2,198-g male baby was delivered at 38 weeks of gestation with characteristic phenotype of Down syndrome of hypertelorism, epicanthic folds and hypoplastic middle phalanx of the fifth fingers. Cytogenetic analysis of cord blood, umbilical cord and placenta revealed a karyotype of 47,XY,+21. QF-PCR analysis of the DNA extracted from placenta revealed double trisomy 5 and trisomy 21 with maternal gene dosage increase in chromosome 5 and chromosome 21.ConclusionPrenatal diagnosis of CPM for trisomy 5 at CVS can be associated with UPD 5 in the fetus, and UPD 5 causes no specific phenotype.     

Prenatal diagnosis of maternal uniparental disomy 16 associated with mosaic trisomy 16 at amniocentesis,and pericardial effusion and intrauterine growth restriction in the fetus

ObjectiveWe present prenatal diagnosis of maternal uniparental disomy (UPD) 16 associated with mosaic trisomy 16 at amniocentesis, and pericardial effusion and intrauterine growth restriction (IUGR) in the fetus.Case reportA 38-year-old woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age, and the result was 47,XX,+16[2]/46,XX[54]. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed 14% mosaicism for trisomy 16 and a paternally inherited 319-kb microdeletion of 15q11.2 encompassing the genes of TUBGCP5, CYFIP1, NIPA2 and NIPA1. Prenatal ultrasound revealed persistent left superior vena cava, pericardial effusion and severe IUGR. Cordocentesis at 23 weeks of gestation revealed a karyotype of 46,XX, but polymorphic DNA marker analysis revealed maternal UPD 16. Repeat amniocentesis was performed at 27 weeks of gestation and revealed a karyotype of 46, XX in 21/21 colonies. Molecular cytogenetic analysis on uncultured amniocytes revealed 22.4% mosaicism (26/116 cells) for trisomy 16 on interphase fluorescence in situ hybridization (FISH) analysis, and 20% mosaicism for trisomy 16 on aCGH. Polymorphic DNA marker analysis on the DNAs extracted from uncultured amniocytes and parental bloods revealed maternal UPD 16. The pregnancy was subsequently terminated, and a fetus was delivered with facial dysmorphism and severe IUGR. The umbilical cord had a karyotype of 47,XX,+16[28]/46,XX[16]. Polymorphic DNA marker analysis on placenta confirmed a maternal origin of trisomy 16.ConclusionCytogenetic discrepancy between cultured amniocytes and uncultured amniocytes may present in mosaic trisomy 16 at amniocentesis. Prenatal diagnosis of mosaic trisomy 16 should alert the association of maternal UPD 16 which may be associated with congenital heart defects and severe IUGR on prenatal ultrasound.     

Low-level mosaic trisomy 9 at amniocentesis associated with a positive non-invasive prenatal testing for trisomy 9, maternal uniparental disomy 9, intrauterine growth restriction and a favorable fetal outcome in a pregnancy

ObjectiveWe present low-level mosaic trisomy 9 at amniocentesis associated with a positive non-invasive prenatal testing (NIPT) for trisomy 9, maternal uniparental disomy (UPD) 9, intrauterine growth restriction (IUGR) and a favorable fetal outcome in a pregnancy.Case reportA 41-year-old, gravida 3, para 0, woman underwent amniocentesis at 18 weeks of gestation because of NIPT at 10 weeks of gestation suspicious of trisomy 9 in the fetus. This pregnancy was conceived by in vitro fertilization (IVF). Amniocentesis revealed a karyotype of 47,XY,+9 [2]/46,XY[23]. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed arr (1–22) × 2, (X,Y) × 1 and detected no genomic imbalance. Polymorphic DNA marker analysis showed maternal uniparental heterodisomy 9 in the amniocytes. Prenatal ultrasound was normal. The woman was referred for genetic counseling at 22 weeks of gestation. The soluble fms-like tyrosine kinase (sFlt)/placental growth factor (PlGF) = 13.1 (normal < 38). There was no gestational hypertension. Continuing the pregnancy was advised. No repeat amniocentesis was performed because of persistent irregular contractions. IUGR was noted. A 2156-g phenotypically normal baby was delivered at 37 weeks of gestation. The cord blood and umbilical cord had a karyotype of 46,XY (40/40 cells). The placenta had a karyotype of 47,XY,+9 (40/40 cells). The parental karyotypes were normal. Quantitative fluorescence polymerase chain reaction (QF-PCR) on the DNA extracted from parental bloods, cord blood, umbilical cord and placenta revealed maternal uniparental heterodisomy 9 in cord blood and umbilical cord, and trisomy 9 of maternal origin in placenta. When follow-up at age three months, the neonate was normal in development and phenotype. The buccal mucosal cells had 3% (3/101 cells) mosaicism for trisomy 9 by interphase fluorescent in situ hybridization (FISH) analysis.ConclusionMosaic trisomy 9 at prenatal diagnosis should alert the possibility of UPD 9 and include a UPD 9 testing. Low-level mosaic trisomy 9 at amniocentesis can be associated with UPD 9 and a favorable fetal outcome.     

Prenatal diagnosis of low-level mosaic trisomy 17 with maternal uniparental disomy 17 by amniocentesis in a pregnancy with a favorable outcome

ObjectiveWe present prenatal diagnosis low-level mosaic trisomy 17 with maternal uniparental disomy (UPD) 17 at amniocentesis in a pregnancy with a favorable outcome.Materials and methodsA 40-year-old, primigravid woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age. This pregnancy was conceived by in vitro fertilization and embryo transfer. Amniocentesis revealed a karyotype of 47,XX,+17 [13]/ 46, XX [23]. Repeat amniocentesis was performed at 21 weeks of gestation. Conventional cytogenetic analysis was applied on cultured amniocytes, parental bloods and cord blood. Simultaneous molecular genetic analysis such as interphase fluorescence in situ hybridization (FISH), array comparative genomic hybridization (aCGH) and quantitative fluorescent polymerase chain reaction (QF-PCR) assays were applied on uncultured amniocytes. Interphase FISH was applied on postnatal buccal cells.ResultsRepeat amniocentesis revealed a karyotype of 47,XX,+17[6]/46,XX[28]. Genetic analyses on uncultured amniocytes showed the results of mosaic trisomy 17 (12/101 cells = 11.9%) in FISH analysis, no genomic imbalance in aCGH analysis and maternal UPD 17 in QF-PCR assays. The parental karyotypes were normal. Prenatal ultrasound findings were unremarkable. The parents decided to continue the pregnancy, and a 1449-g, phenotypically normal female baby was delivered prematurely at 31 weeks of gestation. The cord blood had a karyotype of 46,XX. She had a normal psychomotor development at age 22 months at follow-up. Interphase FISH analysis on buccal cells showed trisomy 17 signals in 1/66 cells (1.5%).ConclusionsLow-level mosaicism for trisomy 17 associated with maternal UPD 17 detected by amniocentesis without ultrasound abnormality can be associated with a favorable outcome. Molecular genetic analysis of uncultured amniocytes at repeat amniocentesis is useful for confirmation and genetic counseling under such as circumstance.     

Detection of maternal uniparental disomy 9 in association with low-level mosaic trisomy 9 at amniocentesis in a pregnancy associated with intrauterine growth restriction,abnormal first-trimester screening result (low PAPP-A and low PlGF), maternal preeclampsia and a favorable outcome

ObjectiveWe present detection of maternal uniparental disomy (UPD) 9 in association with low-level mosaic trisomy 9 at amniocentesis in a pregnancy associated with intrauterine growth restriction (IUGR), an abnormal first-trimester maternal serum screening result, abnormal non-invasive prenatal testing (NIPT), maternal preeclampsia and a favorable outcome.Case reportA 37-year-old, primigravid woman underwent first-trimester maternal serum screening and NIPT at 11 weeks of gestation, which revealed a gene dosage increase in chromosome 9 and low levels of plasma protein-A (PAPP-A) and placental growth factor (PlGF) in maternal blood. The woman underwent amniocentesis at 16 weeks of gestation, which revealed a karyotype of 47,XX,+9[4]/46,XX[35] in cultured amniocytes. Simultaneous array comparative genomic hybridization (aCGH) analysis on uncultured amniocytes revealed a result of arr [GRCh37] (9) × 3 [0.14] (X) × 2, compatible with mosaic trisomy 9. The parental karyotypes were normal. Repeat amniocentesis was performed at 20 weeks of gestation. The cultured amniocytes had a karyotype of 47,XX,+9[1]/46,XX[23]. The uncultured amniocytes had a mosaic trisomy 9 level of 10.7% (12/112 cells) by interphase fluorescence in situ hybridization (FISH), a mosaic trisomy 9 level of 10–14% (log₂ ratio = 0.1) by aCGH, and maternal uniparental isodisomy 9 by polymorphic DNA marker analysis. Prenatal ultrasound revealed IUGR, and the mother had preeclampsia. At 29 weeks of gestation, a 1054-g phenotypically normal baby was delivered because of preterm labor. The cord blood and umbilical cord had the karyotype of 46, XX and maternal UPD 9 and isodisomy 9, while the placenta had trisomy 9 of maternal origin. Postnatal FISH anlaysis on 101 buccal mucosal cells and 100 urinary cells at age three months detected no trisomy 9 signals. The baby was doing well at age six months.ConclusionPregnancy with low-level mosaic trisomy 9 and maternal UPD 9 at amniocentesis can be associated with IUGR, maternal preeclampsia and a favorable outcome. Fetuses with maternal UPD 9 can be associated with an abnormal NIPT result concerning chromosome 9, an abnormal first-trimester maternal serum screening result (low PAPP-A and low PlGF) and mosaic trisomy 9 at amniocentesis.     

Mosaic trisomy 21 at amniocentesis in a twin pregnancy associated with a favorable fetal outcome,maternal uniparental disomy 21 and postnatal decrease of the trisomy 21 cell line

ObjectiveWe present mosaic trisomy 21 at amniocentesis in a twin pregnancy associated with a favorable fetal outcome, maternal uniparental disomy (UPD) 21 and postnatal decrease of the trisomy 21 cell line.Case reportA 36-year-old woman underwent elective amniocentesis at 16 weeks of gestation because of advanced maternal age, and an abnormal non-invasive prenatal testing (NIPT) result suggesting trisomy 21. Amniocentesis revealed the karyotype of 46, XX in co-twin A and the karyotype of 47,XY,+21[12]/46,XY[21] in co-twin B in the cultured amniocytes by in situ culture method. Simultaneous array comparative genomic hybridization (aCGH) analysis on uncultured amniocytes revealed the result of arr (21) × 3 [0.40] in co-twin B, consistent with 40% mosaicism for trisomy 21. Prenatal ultrasound was unremarkable, and the parental karyotypes were normal. Following genetic counseling, the parents decided to continue the pregnancy. At 36 weeks of gestation, a 2140-g female co-twin A and a 1800-g male co-twin B were delivered without any phenotypical abnormality. The karyotypes of the umbilical cord and placenta of co-twin B were 47,XY,+21[16]/46,XY[24] and 47,XY,+21 (40/40 cells), respectively. Quantitative fluorescence polymerase chain reaction (QF-PCR) analysis on the DNA extracted from parental bloods and umbilical cord, cord blood and placenta and peripheral blood at age five months of co-twin B confirmed a maternal origin of trisomy 21 and maternal uniparental isodisomy 21. aCGH analysis on the cord blood revealed the result of arr 21q11.2q22.3 × 2.25 consistent with 20%–25% (log₂ ratio = 0.15–0.2) mosaicism for trisomy 21. When follow-up at age five months, the co-twin B was phenotypically normal. His peripheral blood had a karyotype of 47,XY,+21[3]/46,XY[37]. Interphase fluorescence in situ hybridization (FISH) on 100 buccal mucosal cells detected no trisomy 21 signals. The peripheral blood had uniparental isodisomy 21.ConclusionMosaic trisomy 21 at amniocentesis can be a transient and benign condition and should alert the possibility of UPD 21. The abnormal trisomy 21 cell line in mosaic trisomy 21 at amniocentesis may decrease and disappear after birth.     

Prenatal diagnosis of low-level mosaic trisomy 20 by amniocentesis in a pregnancy with a favorable outcome

ObjectiveWe present prenatal diagnosis of low-level mosaic trisomy 20 by amniocentesis in a pregnancy with a favorable outcome.Case reportA 35-year-old woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 47,XX,+20[8]/46,XX[23]. The parental karyotypes were normal, and prenatal ultrasound findings were unremarkable. Repeat amniocentesis performed at 20 weeks of gestation revealed a karyotype of 47,XX,+20[2]/46,XX[19]. Simultaneous molecular cytogenetic tests using uncultured amniocytes revealed no genomic imbalance in array comparative genomic hybridization (aCGH) analysis and a mosaic level of 14.3% (15/105 cells) in interphase fluorescence in situ hybridization (FISH) analysis. Polymorphic DNA marker analysis using the DNAs extracted from uncultured amniocytes and parental bloods excluded uniparental disomy 20. At 39 weeks of gestation, a phenotypically normal 3580-g female baby was delivered without any structural abnormality. The neonate was doing well at age two years during postnatal follow-ups. Her psychomotor development was normal. Interphase FISH analysis of urinary cells revealed no trisomy 20 signals in 45/45 urinary cells. The peripheral blood had a karyotype of 46,XX in 40/40 lymphocytes.ConclusionFetuses with low-level mosaic trisomy 20 at amniocentesis can have a favorable outcome. Molecular cytogenetic analysis on uncultured amniocytes is useful for confirmatory diagnosis of the mosaic level in case of mosaic trisomy 20 at amniocentesis with different mosaic levels at different amniocenteses.     

Low-level mosaic trisomy 15 at amniocentesis without uniparental disomy 15 in a pregnancy associated with cytogenetic discrepancy between uncultured amniocytes and cultured amniocytes,a favorable fetal outcome and perinatal decrease of the aneuploid cell line

ObjectiveWe present low-level mosaic trisomy 15 without uniparental disomy (UPD) 15 in a pregnancy associated with cytogenetic discrepancy between uncultured amniocytes and cultured amniocytes, a favorable fetal outcome and perinatal decrease of the aneuploid cell line.Case reportA 40-year-old, gravida 2, para 0, woman underwent amniocentesis at 16 weeks of gestation because advanced maternal age. This pregnancy was conceived by in vitro fertilization and embryo transfer. Amniocentesis revealed a karyotype of 47,XX,+15 [7]/46,XX [43]. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed arr (15) × 2–3 (X) × 2 with 14% mosaicism for trisomy 15, and ME028 multiplex ligation-dependent probe amplification (MLPA) methylation test excluded UPD 15. Prenatal ultrasound and parental karyotypes were normal. She was referred for genetic counseling, and repeat amniocentesis performed at 28 weeks of gestation revealed 46, XX (20/20 colonies) in cultured amniocytes, and in uncultured amniocytes, interphase fluorescence in situ hybridization (FISH) showed 13.7% (16/117 cells) mosaicism for trisomy 15, aCGH analysis revealed arr [GRCh(hg19)] 15q11.22q26.3 (22, 765, 628–102,256,748) × 2.4 with a log₂ ratio = 0.26, consistent with 40% mosaicism for trisomy 15, and quantitative fluorescent polymerase chain reaction (QF-PCR) assays excluded UPD 15. The woman was encouraged to continue the pregnancy. At 37 weeks of gestation, a 2400-g phenotypically normal female baby was delivered without any abnormality. The cord blood had 46, XX (40/40 cells). QF-PCR assays determined maternal origin of trisomy 15 in the placenta. When follow-up at age 5 months, the neonate was normal in physical and psychomotor development. FISH analysis on 102 buccal mucosal cells detected 2 cells (2%, 2/102 cells) with trisomy 15 signals, compared with 1% in normal control.ConclusionsLow-level mosaic trisomy 15 at amniocentesis without UPD 15 can be a transient and benign condition, and can be associated with a favorable fetal outcome and perinatal decrease of the aneuploid cell line.     

Mosaic trisomy 21 at amniocentesis associated with a favorable fetal outcome and perinatal progressive decrease of the trisomy 21 cell line

ObjectiveWe present mosaic trisomy 21 at amniocentesis associated with a favorable fetal outcome and perinatal progressive decrease of the trisomy 21 cell line.Case reportA 33-year-old woman underwent elective amniocentesis at 17 weeks of gestation because of anxiety, and the karyotype of cultured amniocytes was 47,XX,+21[4]/46,XX[13]. In 17 colonies of cultured amniocytes, four colonies had 47,XX,+21, while the other 13 colonies had 46,XX. Simultaneous array comparative genomic hybridization (aCGH) analysis on uncultured amniocytes revealed the result of arr (21) × 3 [0.32] consistent with 32% mosaicism for trisomy 21. Repeat amniocentesis performed at 25 weeks of gestation revealed 47,XX,+21[4]/46,XX[24] with four colonies of 47,XX,+21 and 24 colonies of 46, XX on cultured amniocytes, and arr 21q11.2q22.3 × 2.25 by aCGH, 19.2% mosaicism for trisomy 21 (20/104 cells) by interphase fluorescence in situ hybridization (FISH), and no uniparental disomy (UPD) 21 by quantitative fluorescence polymerase chain reaction (QF-PCR) on uncultured amniocytes. The parental karyotypes were normal, and prenatal ultrasound was unremarkable. A phenotypically normal 2815-g female baby was delivered at 38 weeks of gestation. Cytogenetic analysis on the cord blood, umbilical cord and placenta revealed the karyotype of 47,XX,+21[10]/46,XX[30]. 47,XX,+21[5]/46,XX[35] and 47,XX,+21[38]/46,XX[2], respectively. QF-PCR analysis on the DNA extracted from parental bloods, uncultured amniocytes, cord blood, umbilical cord and placenta confirmed a paternal origin of trisomy 21. When follow-up at age two months, the neonate was phenotypically normal, the peripheral blood had a karyotype of 47,XX,+21[6]/46,XX[34], and no trisomy 21 signals by interphase FISH was found on 100 buccal mucosal cells. When follow-up at age 13 months, the neonate was phenotypically normal, and the peripheral blood had a karyotype of 47,XX,+21[3]/46,XX[37].ConclusionMosaic trisomy 21 at amniocentesis can be a transient and benign condition, and the abnormal trisomy 21 cell line may decrease and disappear after birth.     

Prenatal diagnosis of low-level mosaicism for trisomy 13 at amniocentesis associated with a favorable outcome

Objective

We present prenatal diagnosis of low-level mosaicism for trisomy 13 at amniocentesis associated with a favorable outcome.

Mosaic trisomy 18 at amniocentesis associated with a favorable fetal outcome in a pregnancy

ObjectiveWe present prenatal diagnosis of mosaic trisomy 18 by amniocentesis associated with a favorable fetal outcome in a pregnancy.Case reportA 42-year-old, gravida 4, para 2, woman underwent amniocentesis at 18 weeks of gestation because advanced maternal age. Amniocentesis revealed a karyotype of 47,XX,+18[6]/46,XX[17]. Simultaneous array comparative genomic hybridization (aCGH) on uncultured amniocytes showed the result of 45% mosaicism for trisomy 18. At 25 weeks of gestation, the woman underwent repeat amniocentesis which revealed a karyotype of 47,XX,+18[10]/46,XX[24]. Simultaneous aCGH on uncultured amniocytes showed the result of arr 18p11.32q23 (148,963–78,012,829) × 2.3 [GRCh (hg19)] with a log₂ ratio of 0.2–0.25 compatible with 30–38% mosaicism for trisomy 18. The parental karyotypes were normal. Prenatal ultrasound was unremarkable. Interphase fluorescence in situ hybridization (FISH) on uncultured amniocytes showed 27% (27/100 cells) mosaicism for trisomy 18. Quantitative fluorescent polymerase chain reaction (QF-PCR) on uncultured amniocytes excluded uniparental disomy (UPD) 18. Non-invasive prenatal testing (NIPT) analysis at 34 weeks of gestation revealed a significant gene dosage increase of chromosome 18 (29.95; normal control: ?3.0–3.0). At 39 weeks of gestation, a 2840-g phenotypically normal baby was delivered. The cord blood had a karyotype of 47,XX,+18[8]/46,XX[32]. The placenta was trisomy 18 of maternal origin. The umbilical cord had a karyotype of 47,XX,+18[2]/46,XX[38]. At age 1½ months, the peripheral blood had a karyotype of 47,XX,+18[5]/46,XX[35], and FISH analysis on buccal mucosal cells revealed 2% (2/102 cells) mosaicism for trisomy 18. When follow-up at age seven months, the neonate was phenotypically normal, and the peripheral blood had a karyotype of 47,XX,+18[1]/46,XX[39].ConclusionsMosaic trisomy 18 at amniocentesis without abnormal fetal ultrasound can be associated with a favorable outcome, and the abnormal trisomy 18 cell line may decrease progressively after birth.     

Late amniocentesis with uniparental disomy testing following successful in vitro fertilization and transfer of three mosaic embryos in a pregnancy with a favorable outcome

ObjectiveWe present late amniocentesis with the application of uniparental disomy (UPD) testing following successful in vitro fertilization (IVF) and transfer of three mosaic embryos in a pregnancy with a favorable outcome.Case reportA 41-year-old, gravida 2, para 0, woman underwent late amniocentesis at 28 weeks of gestation because of advanced maternal age. The pregnancy was conceived by IVF and transfer of three mosaic embryos, i.e., one embryo with mosaic trisomies 20 and 2, one embryo with mosaic partial trisomies 9 and 3 and one embryo with partial trisomies 11 and 17. First-trimester non-invasive prenatal testing (NIPT) and fetal ultrasound revealed no abnormal findings. Late amniocentesis revealed a karyotype of 46,XY. Array comparative genomic hybridization (aCGH) revealed the result of arr [GRCh37] (X,Y) × 1, (1–22) × 2. Polymorphic DNA marker analysis using the DNAs extracted from the uncultured amniocytes and parental bloods excluded UPD 20. At 38 weeks of gestation, a healthy 3010-g male baby was delivered with no phenotypic abnormalities.ConclusionPrenatal diagnosis of normal karyotype following mosaic embryo transfer should include UPD testing if necessary.     

Prenatal diagnosis of trisomy 11 in a single colony of cultured amniocytes at amniocentesis in a pregnancy with a favorable outcome

ObjectiveWe present prenatal diagnosis of trisomy 11 in a single colony of cultured amniocytes at amniocentesis and the perinatal outcome.Case reportA 36-year-old, gravida 2, para 1, woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 47,XX,+11[1]/46,XX[16]. In 17 colonies of cultured amniocytes, all five cells in one colony had a karyotype of 47,XX,+11, while the rest 16 colonies had a normal karyotype. The parental karyotypes were normal. Repeat amniocentesis was performed at 21 weeks of gestation. Interphase fluorescence in situ hybridization (FISH) was applied on the uncultured amniocytes, and the result revealed 0.9% mosaicism (1/101 cells) for trisomy 11 with only one cell with three signals, while the other 100 cells had two signals, compared with no trisomy 11 signals (0/100 cells) in the normal control. Uniparental disomy (UPD) 11 was excluded by polymorphic DNA marker analysis on the DNAs extracted from uncultured amniocytes and parental bloods. The cultured amniocytes at repeat amniocentesis revealed a karyotype of 46, XX in 28/28 colonies. Prenatal ultrasound findings were unremarkable. The pregnancy was continued to 38 weeks of gestation, and a 2724-g healthy female baby was delivered. The cord blood had a karyotype of 46,XX. The interphase FISH analysis on buccal mucosal cells revealed no trisomy 11 signals (0/100 cells). When follow-up at three months of age, the neonate manifested normal psychomotor and physical development.ConclusionPrenatal diagnosis of mosaic trisomy 11 in a single colony at amniocentesis without abnormal fetal ultrasound and UPD 11 can be associated with a favorable outcome.     

Cytogenetic discrepancy between uncultured amniocytes and cultured amniocytes in mosaic trisomy 18 at amniocentesis in a pregnancy with a favorable fetal outcome and maternal uniparental disomy 18

ObjectiveWe present prenatal diagnosis of mosaic trisomy 18 in a pregnancy with a favorable fetal outcome and maternal uniparental disomy 18.Case reportA 38-year-old, primigravid woman underwent the first amniocentesis at 16 weeks of gestation because advanced maternal age. Amniocentesis revealed a karyotype of 46,XX [22/22] in cultured amniocytes, and 36% mosaicism for trisomy 18 and a maternally inherited Xp22.31 microdeletion by array comparative genomic hybridization (aCGH) in uncultured amniocytes. The second amniocentesis at 18 weeks of gestation revealed 47,XX,+18 [14]/46,XX [36] in cultured amniocytes and 36% mosaicism for trisomy 18 by multiplex ligation-dependent probe amplification (MLPA) P095 in cultured amniocytes. Prenatal ultrasound was normal. The parents were phenotypically normal. The third amniocentesis at 23 weeks of gestation revealed 47,XX,+18 [3]/46,XX [17] in cultured amniocytes, and in uncultured amniocytes, aCGH revealed 45%–50% mosaicism for trisomy 18, interphase fluorescence in situ hybridization (FISH) revealed 36% (36/100 cells) mosaicism for trisomy 18, and quantitative fluorescent polymerase chain reaction (QF-PCR) showed mosaic maternal uniparental heterodisomy for chromosome 18 and mosaic trisomy 18 of maternal origin. The fourth amniocentesis at 32 weeks of gestation revealed a karyotype of 46,XX [20/20] in cultured amniocytes, and in uncultured amniocytes, aCGH revealed 50%–60% mosaicism for trisomy 18, FISH revealed 21.8% (22/101 cells) mosaicism for trisomy 18, and non-invasive prenatal testing (NIPT) showed chromosome 18 gene dosage increase in the maternal blood. At 34 weeks of gestation, a 1480-g phenotypically normal baby was delivered. The cord blood had 47,XX,+18 [10]/46,XX [30]. The umbilical cord had 47,XX,+18 [4]/46,XX [36]. The placenta had 47,XX,+18 [40/40], and QF-PCR analysis confirmed trisomy 18 of maternal origin. When follow-up at age four months, the neonate was phenotypically normal, FISH analysis on buccal mucosal cells revealed 2% (2/100 cells) mosaicism for trisomy 18, and the peripheral blood had 47,XX,+18 [18]/46,XX [22]. When follow-up at age eight months, the neonate had normal development, the peripheral blood had 47,XX,+18 [15]/46,XX [25], and the buccal mucosal cells showed maternal uniparental heterodisomy for chromosome 18.ConclusionCytogenetic discrepancy may occur between uncultured and cultured amniocytes in mosaic trisomy 18 at amniocentesis. Cultured amniocytes may present progressive decrease in the levels of mosaicism for trisomy 18 as the fetus grows. Mosaic trisomy 18 at amniocentesis can be associated with a favorable outcome.     

Low-level mosaic trisomy 21 at amniocentesis in a pregnancy associated with a negative NIPT result,cytogenetic discrepancy in various tissues,perinatal progressive decrease of the aneuploid cell line and a favorable fetal outcome

ObjectiveWe present low-level mosaic trisomy 21 at amniocentesis associated with a favorable fetal outcome.Case reportA 31-year-old primigravid woman underwent non-invasive prenatal testing (NIPT) at 12 weeks of gestation, and the result was normal. She underwent amniocentesis at 16 weeks of gestation because of fetal choroid plexus cyst, and the result was 47,XX,+21[5]/46,XX[32]. Repeat amniocentesis was performed at 19 weeks of gestation, and the result was 47,XX,+21[5]/46,XX[15]. Simultaneous array comparative genomic hybridization (aCGH) analysis on uncultured amniocytes revealed the result of arr (21) × 3 [0.10], consistent with 10% mosaicism for trisomy 21. Prenatal ultrasound findings were unremarkable. She was referred for genetic counseling at 22 weeks of gestation, and the third amniocentesis was performed at 25 weeks of gestation, and the result was 46,XX (20/20 colonies). The parental karyotypes were normal. Simultaneous quantitative fluorescence polymerase chain reaction (QF-PCR) analysis on the DNA extracted from uncultured amniocytes and parental bloods excluded uniparental disomy (UPD) 21. aCGH analysis on uncultured amniocytes revealed arr 21q11.2q22.3 × 2.1 (log₂ ratio = 0.1), consistent with 10–15% mosaicism for trisomy 21. Fluorescence in situ hybridization (FISH) analysis on uncultured amniocytes revealed 30% (30/100 cells) mosaicism for trisomy 21. The woman was advised to continue the pregnancy, and a phenotypically normal 2800-g female baby was delivered at 38 weeks of gestation. The karyotype of cord blood, umbilical cord and placenta were 47,XX,+21[1]/46,XX[39]. 47,XX,+21[4]/46,XX[36] and 46,XX (40/40 cells), respectively. When follow-up at age two months, the neonate was phenotypically normal. The peripheral blood had a karyotype of 47,XX,+21[1]/46,XX[39], and FISH analysis on buccal mucosal cells revealed 8.4% (7/83 cells) mosaicism for trisomy 21, compared with 0% in the normal control.ConclusionLow-level mosaic trisomy 21 at amniocentesis can be associated with a negative NIPT result, cytogenetic discrepancy in various tissues, perinatal progressive decrease of the aneuploid cell line and a favorable fetal outcome.     

Low-level mosaic trisomy 20 without uniparental disomy 20 at amniocentesis in a pregnancy associated with a favorable outcome,cytogenetic discrepancy between uncultured amniocytes and cultured amniocytes and perinatal progressive decrease of the aneuploid cell line

ObjectiveWe present low-level mosaic trisomy 20 without uniparental disomy (UPD) 20 at amniocentesis in a pregnancy associated with a favorable outcome, cytogenetic discrepancy between uncultured amniocytes and cultured amniocytes and perinatal progressive decrease of the aneuploid cell line.Case reportA 36-year-old, gravida 2, para 1, woman underwent amniocentesis at 16 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 47,XY,+20[3]/46,XY[17]. Array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed the result of arr (1–22) × 2, X × 1, Y × 1 with no genomic imbalance. Prenatal ultrasound was unremarkable. She was referred for genetic counseling at 23 weeks of gestation, and repeat amniocentesis was performed. Cytogenetic analysis of the cultured amniocytes revealed a karyotype of 47,XY,+20[1]/46,XY[27]. Simultaneous aCGH analysis on the DNA extracted from uncultured amniocytes by SurePrint G3 Unrestricted CGH ISCA v2, 8 × 60 K (Agilent Technologies, CA, USA) revealed the result of arr (1–22) × 2, X × 1, Y × 1. Quantitative fluorescent polymerase chain reaction (QF-PCR) assays on the DNAs extracted from uncultured amniocytes and parental bloods excluded UPD 20. The woman was advised to continue the pregnancy, and a healthy 3750-g phenotypically normal male baby was delivered at 38 weeks of gestation. The cord blood had a karyotype of 46,XY (40/40 cells).ConclusionLow-level mosaic trisomy 20 without UPD 20 at amniocentesis can be associated with a favorable outcome. Progressive decrease of the aneuploid cell line can occur in mosaic trisomy 20 at amniocentesis. Low-level mosaic trisomy 20 at amniocentesis can be a transient and benign condition.     

Prenatal diagnosis of pseudomosaicism for trisomy 20 at amniocentesis with a negative non-invasive prenatal testing (NIPT) result in a pregnancy with a favorable outcome

ObjectiveWe present prenatal diagnosis of pseudomosaicism for trisomy 20 at amniocentesis with a negative non-invasive prenatal testing (NIPT) result in a pregnancy with a favorable outcome.Case reportA 33-year-old, primigravid woman underwent amniocentesis at 17 weeks of gestation, which revealed a karyotype of 47,XX,+20[8]/46,XX[31]. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed the result of arr (1–22,X) × 2, consistent with no genomic imbalance. She was referred to the hospital for repeat amniocentesis at 23 weeks of gestation. At repeat amniocentesis, cultured amniocytes had a karyotype of 47,XX,+20[2]/46,XX[33]. The parental karyotypes were normal. Simultaneous aCGH analysis on the DNA extracted from uncultured amniocytes using SurePrint G3 Unrestricted CGH ISCA v2, 8 × 60 K (Agilent Technologies, Santa Clara, CA, USA) revealed no genomic imbalance, or arr (1–22,X) × 2, Y × 0. Interphase fluorescence in situ hybridization (FISH) analysis using the bacterial artificial chromosome (BAC) probes of RP11-266K16 [20q13.33; fluorescein isothiocyanate (FITC), spectrum green] and RP11-348I14 (20q11.1-q11.21; Texas Red, spectrum red) detected trisomy 20 signals in 4/104 uncultured amniocytes (3.8%), compared with 0/100 in the normal control. Polymorphic DNA marker analysis using the DNA extracted from uncultured amniocytes and parental bloods excluded uniparental disomy 20. NIPT analysis on maternal blood revealed a negative result without gene dosage increase in chromosome 20. The pregnancy was carried to term, and a healthy 2830-g female baby was delivered with no phenotypic abnormality. Both cord blood and placenta had a karyotype of 46,XX.ConclusionNIPT is useful for rapid differential diagnosis of pseudomosaicism from true mosaicism in case of mosaic trisomy 20 at amniocentesis.     

Prenatal diagnosis and molecular cytogenetic characterization of low-level mosaicism for tetrasomy 18p at amniocentesis in a pregnancy with a favorable outcome

Objective

We present prenatal diagnosis of low-level mosaicism for tetrasomy 18p at amniocentesis in a pregnancy with a favorable outcome.