Low-level mosaicism for trisomy 16 at amniocentesis in a pregnancy associated with intrauterine growth restriction and a favorable outcome

ObjectiveWe present low-level mosaicism for trisomy 16 at amniocentesis in a pregnancy associated with intrauterine growth restriction (IUGR) and a favorable outcome.Case reportA 31-year-old woman underwent amniocentesis at 24 weeks of gestation because of IUGR. Amniocentesis revealed a karyotype of 47,XX,+16 [3]/46,XX [22]. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed gene dosage increase in chromosome 16 consistent with 28% mosaicism for trisomy 16. Uniparental disomy (UPD) 7 and UPD 11 were excluded. She underwent repeat amniocentesis at 27 weeks of gestation. Repeat amniocentesis revealed a karyotype of 47,XX,+16 [1]/46,XX [24]. Simultaneous aCGH analysis on the DNA extracted from uncultured amniocytes revealed 25%–35% (log₂ ratio = 0.17–0.25) mosaicism for trisomy 16. Interphase fluorescence in situ hybridization (FISH) analysis detected trisomy 16 signals in 28/100 (28%) uncultured amniocytes. Polymorphic DNA marker analysis excluded UPD 16. Level II ultrasound revealed no fetal abnormalities except symmetric IUGR. The pregnancy was continued to 37 weeks of gestation, and a 2306-g phenotypically normal baby was delivered. The cord blood had a karyotype of 46, XX in 50/50 lymphocytes. The umbilical cord had a karyotype of 47,XX,+16 [14]/46,XX [36]. Interphase FISH analysis on buccal mucosal cells and urinary cells at age three days revealed trisomy 16 signals in 3.8% (4/106) buccal mucosal cells and 6.5% (7/107) urinary cells, compared with 1% in the normal control. Polymorphic DNA marker analysis on placenta confirmed trisomy 16 in the placenta and a maternal origin of the extra chromosome 16.ConclusionCytogenetic discrepancy between cultured amniocytes and uncultured amniocytes may present in mosaic trisomy 16 at amniocentesis. Low-level mosaicism for trisomy 16 at amniocentesis without maternal UPD 16 can be associated with a favorable outcome despite the presence of IUGR.     

Cytogenetic discrepancy between uncultured amniocytes and cultured amniocytes in mosaic trisomy 15 at amniocentesis in a pregnancy with a favorable outcome

ObjectiveWe present prenatal diagnosis of mosaic trisomy 15 in a pregnancy with a favorable outcome.Case reportA 33-year-old, primigravid woman underwent amniocentesis at 19 weeks of gestation because non-invasive prenatal testing (NIPT) revealed gene dosage increase at chromosome 15. Cytogenetic analysis revealed a karyotype of 47,XX,+15[10]/46,XX[13]. Using uncultured amniocytes, array comparative genomic hybridization (aCGH) revealed arr [GRCh37] (X) × 2, (15) × 3 [0.75], multiplex ligation-dependent probe amplification (MLPA) analysis showed rsa [GRCh36] 15q11q13 (21,362,818–27,196,819) × 3 [0.76] and methylation-specific (MS)-MLPA analysis showed a methylation index = 0.41 with paternal gene dosage increase at 15q11-q13. Repeat amniocentesis at 25 weeks of gestation revealed a karyotype of 47,XX,+15[6]/46,XX[14]. Using uncultured amniocytes, quantitative fluorescent polymerase chain reaction (QF-PCR) assays excluded uniparental disomy (UPD) 15 and determined a paternal origin of the extra chromosome 15, aCGH analysis showed 75%–80% mosaicism for trisomy 15, and interphase fluorescence in situ hybridization (FISH) showed 45.5% (46/101 cells) mosaicism for trisomy 15. Repeat amniocentesis at 28 weeks of gestation revealed a karyotype of 47,XX,+15[2]/46,XX[23]. Using uncultured amniocytes, aCGH showed 75–80% mosaicism for trisomy 15, and FISH showed 70.6% (72/102 cells) mosaicism for trisomy 15. Using cultured amniocytes, QF-PCR assays excluded UPD 15. Cordocentesis at 30 weeks of gestation revealed a karyotype of 47,XX,+15[2]/46,XX[138]. Using cord blood, aCGH revealed 9% gene dosage increase at chromosome 15, and MS-MLPA analysis excluded UPD 15. At 36 weeks of gestation, a 2060-g phenotypically normal baby was delivered. The cord blood had 46, XX (40/40 cells). The placenta had 47,XX,+15 (40/40 cells). QF-PCR analysis on placenta showed a paternal origin of trisomy 15. FISH analysis on buccal mucosal cells at age 20 days showed 20% (20/100 cells) mosaicism for trisomy 15.ConclusionCytogenetic discrepancy may occur between uncultured and cultured amniocytes in mosaic trisomy 15 at amniocentesis. Cultured amniocytes may present progressive decrease in the levels of mosaicism for trisomy 15 as the fetus grows. Mosaic trisomy 15 at amniocentesis without UPD 15 can be 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.     

Prenatal diagnosis of mosaicism for double trisomies of trisomy 11 and trisomy 12 in a single colony at amniocentesis in a pregnancy with a favorable outcome

ObjectiveWe present prenatal diagnosis of mosaicism for double trisomies of trisomy 11 and trisomy 12 in a single colony at amniocentesis with a favorable outcome.Case reportA 23-year-old woman underwent amniocentesis at 24 weeks of gestation because of congenital bowel dilation in the fetus. Amniocentesis revealed a karyotype of 48,XX,+11,+12[1]/46,XX[24]. In 25 colonies of cultured amniocytes, all five cells in one colony had the karyotype of 48,XX,+11,+12, while the rest 24 colonies had the karyotype of 46,XX. The parental karyotypes were normal. Repeat amniocentesis was performed at 26 weeks of gestation. Interphase fluorescence in situ hybridization (FISH), array comparative genomic hybridization (aCGH) and quantitative fluorescent polymerase chain reaction (QF-PCR) were applied on the uncultured amniocytes, and conventional cytogenetic analysis was applied on cultured amniocytes. Interphase FISH analysis showed no trisomy 11 signal and no trisomy 12 signal in 102 uncultured amniocytes. QF-PCR analysis excluded uniparental disomy (UPD) 11 and UPD 12. aCGH analysis showed no genomic imbalance. The cultured amniocytes at repeat amniocentesis had the karyotype of 46,XX in 13/13 colonies. At term, a healthy 3445-g female baby was delivered with no phenotypic abnormality except imperforate anus and a perianal fistula. The cord blood had a karyotype of 46,XX in 40/40 lymphocytes. Postnatal interphase FISH analysis of buccal cells and urinary cells revealed trisomies 11 and 12 signals in 11/111 (9.9%) buccal cells compared with 3% in normal control, and in 3/103 (2.9%) urinary cells compared with 0.98% in normal control.ConclusionMosaicism for double trisomies of trisomy 11 and trisomy 12 in a single colony at amniocentesis without UPD 11 and UPD 12 can be associated with a favorable outcome.     

Mosaic trisomy 12 at amniocentesis: Prenatal diagnosis and molecular genetic analysis

ObjectiveThis study is aimed at prenatal diagnosis of mosaic trisomy 12 and reviewing the literature.Materials and MethodsA 34-year-old woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Cytogenetic analysis of cultured amniocytes revealed a karyotype of 47,XX,+12[9]/46,XX[14]. She was referred to the hospital for genetic counseling. Repeated amniocentesis was performed at 22 weeks of gestation. Array comparative genomic hybridization (aCGH), interphase fluorescence in situ hybridization (FISH) and quantitative fluorescent polymerase chain reaction (QF-PCR) were applied on uncultured amniocytes, and conventional cytogenetic analysis was applied on cultured amniocytes.ResultsThe aCGH analysis on uncultured amniocytes revealed a small genomic gain in chromosome 12. Interphase FISH analysis on uncultured amniocytes using a 12q11-q12-specific probe of RP11-496H24 (green spectrum) showed three green signals in 17.8% (8/45 cells) of uncultured amniocytes. QF-PCR analysis on uncultured amniocytes using chromosome 12-specific microsatellite markers excluded uniparental disomy 12. Cytogenetic analysis of cultured amniocytes revealed a karyotype of 47,XX,+12[5]/46,XX[25]. The parents decided to continue the pregnancy. A healthy 3270 g female baby was delivered at 39 weeks of gestation, with no phenotypic abnormalities. Cytogenetic analysis of the cord blood revealed a karyotype of 46,XX in 40/40 cultured lymphocytes. The neonate was normal in growth and psychomotor development at 6 months of age. Interphase FISH analysis on uncultured urinary cells revealed 5% (1/20 cells) mosaicism for trisomy 12.ConclusionPrenatal diagnosis of mosaic trisomy 12 at amniocentesis should alert a clinically significant aneuploidy. Interphase FISH and aCGH on uncultured amniocytes are useful for rapid confirmation of low-level trisomy 12 mosaicism at repeated amniocentesis.     

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.     

Cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes in mosaic double trisomy involving trisomy 7 and trisomy 20 (48,XY,+7,+20) at amniocentesis

ObjectiveWe present mosaic double trisomy involving trisomy 7 and trisomy 20 at amniocentesis in a pregnancy with a favorable outcome.Case reportA 41-year-old woman underwent amniocentesis at 16 weeks of gestation because of advanced maternal age. Amniocentesis revealed a result of 48,XY,+7,+20[6]/46,XY[26] in cultured amniocytes. At 19 weeks of gestation, repeat amniocentesis was performed, which revealed a result of 48,XY,+7,+20[4]/46,XY[21] in cultured amniocytes. Simultaneous molecular cytogenetic analyses on uncultured amniocytes at repeat amniocentesis revealed no genomic imbalance in array comparative genomic hybridization (aCGH) analysis, no trisomy 7 and no trisomy 20 signals in 114/114 cells in interphase fluorescence in situ hybridization (FISH) analysis, and no uniparental disomy (UPD) 7 and no UPD 20 in quantitative fluorescent polymerase chain reaction (QF-PCR) analysis. Interphase FISH analysis on cultured amniocytes revealed double trisomy of trisomy 7 and trisomy 20 in 5/105 cells (4.7%) compared with 0/100 cells (0%) in the normal control. Prenatal ultrasound findings were unremarkable. The parental karyotypes were normal. The woman decided to continue the pregnancy, and a healthy 2880-g phenotypically normal male baby was delivered at 34 weeks of gestation without any structural abnormality. The cord blood had a normal karyotype. Interphase FISH analysis of the urinary cells revealed no trisomy 7 and no trisomy 20 signals in 51/51 urinary cells.ConclusionCytogenetic discrepancy between cultured amniocytes and uncultured amniocytes can occur in mosaicism for double trisomy involving trisomy 7 and trisomy 20 at amniocentesis. Molecular cytogenetic analyses such as aCGH, FISH and QF-PCR on uncultured amniocytes are useful for rapid distinguishing true mosaicism from pseudomosaicism under such a circumstance.     

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 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.     

Low-level mosaic trisomy 17 at amniocentesis in a pregnancy associated with a favorable fetal outcome and cytogenetic discrepancy between cultured and uncultured amniocytes

ObjectiveWe present low-level mosaic trisomy 17 at amniocentesis in a pregnancy associated with a favorable fetal outcome and cytogenetic discrepancy between cultured and uncultured amniocytes.Case reportA 32-year-old, primigravid woman underwent amniocentesis at 18 weeks of gestation because of an increased nuchal translucency thickness of 3 mm in the first trimester sonographic screening. Amniocentesis revealed a karyotype of 47,XX,+17 [2]/46,XX [20]. Among 22 colonies of cultured amniocytes, two colonies had a karyotype of 47,XX,+17, whereas the rest 20 colonies had a karyotype of 46,XX. Simultaneous array comparative genomic hybridization (aCGH) on the DNA extracted from uncultured amniocytes revealed arr (1–22,X) × 2 with no genomic imbalance. Prenatal ultrasound and parental karyotypes were normal. Quantitative fluorescence polymerase chain reaction (QF-PCR) analysis on the DNA extracted from the parental bloods and cultured amniocytes excluded uniparental disomy (UPD) 17. The woman was encouraged to continue the pregnancy. A normal 3178-g female baby was delivered at 38 weeks of gestation without any phenotypic abnormalities. The karyotypes of cord blood, umbilical cord and placenta were all 46, XX (40/40 cells). When follow-up at age six months, the neonate was normal in physical and psychosomatic development.ConclusionLow-level mosaic trisomy 17 at amniocentesis can be a transient and benign condition, and can be associated with a favorable fetal outcome and cytogenetic discrepancy between cultured and uncultured amniocytes.     

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 double trisomy involving trisomy 6 and trisomy 20 (48,XY,+6,+20) at amniocentesis without uniparental disomy (UPD) 6 and UPD 20 in a pregnancy associated with a favorable outcome

ObjectiveWe present low-level mosaic double trisomy involving trisomy 6 and trisomy 20 (48,XY,+6,+20) at amniocentesis without uniparental disomy (UPD) 6 and UPD 20 in a pregnancy associated with a favorable outcome.Case reportA 38-year-old woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 48,XY,+6,+20[2]/46,XY[15]. Repeat amniocentesis at 20 weeks of gestation revealed a karyotype of 48,XY,+6,+20[6]/46,XY[43], and simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed the result of arr (X,Y) × 1, (1–22) × 2 with no genomic imbalance. At 22 weeks of gestation, the woman underwent cordocentesis which revealed karyotype of 46,XY (60/60 cells). At 26 weeks of gestation, the woman underwent the third amniocentesis which revealed a karyotype of 48,XY,+6,+20[5]/46,XY[30], and simultaneous aCGH analysis on the DNA extracted from uncultured amniocytes revealed the result of arr (1–22) × 2, X × 1, Y × 1 without genomic imbalance. The parental karyotypes and prenatal ultrasound were normal. Polymorphic marker analysis using the DNAs extracted from uncultured amniocytes and parental bloods excluded UPD 6 and UPD 20. Interphase fluorescence in situ hybridization (FISH) analysis on 100 uncultured amniocytes detected double trisomy 6 and trisomy 20 in 10 cells, consistent with 10% (10/100 cells) mosaicism for double trisomy 6 and trisomy 20. The woman was encouraged to continue the pregnancy, and a phenotypically normal 3328-g male baby was delivered at 38 weeks of gestation. The cord blood, umbilical cord and the placenta had a karyotype of 46,XY (40/40 cells).ConclusionLow-level mosaic double trisomy involving trisomy 6 and trisomy 20 at amniocentesis without UPD 6 and UPD 20 can be associated with a favorable fetal outcome.     

Low-level mosaic trisomy 9 at amniocentesis in a pregnancy associated with a favorable fetal outcome,intrauterine growth restriction,cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes and perinatal progressive decrease of the aneuploid cell line

ObjectiveWe present low-level mosaic trisomy 9 at amniocentesis in a pregnancy associated with a favorable fetal outcome, intrauterine growth restriction (IUGR), cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes and perinatal progressive decrease of the aneuploid cell line.Case reportA 37-year-old, primigravid woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. This pregnancy was conceived by in vitro fertilization and embryo transfer (IVF-ET). Amniocentesis revealed a karyotype of 47,XY,+9[11]/46,XY[32], and simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed arr (X,Y) × 1, (1–22) × 2 without genomic imbalance. Prenatal ultrasound and parental karyotypes were normal. Repeat amniocentesis at 22 weeks of gestation revealed a karyotype of 47,XY,+9[5]/46,XY[19], and simultaneous aCGH analysis on the DNA extracted from uncultured amniocytes revealed arr 9p24.3q34.3 × 2.1 (log₂ ratio = 0.1) compatible with 10–15% mosaicism for trisomy 9. Quantitative fluorescence polymerase chain reaction (QF-PCR) assays excluded uniparental disomy (UPD) 9. A third amniocentesis at 29 weeks of gestation revealed a karyotype of 47,XY,+9[5]/46,XY[18], and simultaneous aCGH analysis on the DNA extracted from uncultured amniocytes revealed arr 9p24.3q34.3 × 2.1 (log₂ ratio = 0.1) compatible with 10–15% mosaicism for trisomy 9. Interphase fluorescent in situ hybridization (FISH) analysis on uncultured amniocytes revealed 9% (9/100 cells) mosaicism for trisomy 9. IUGR was noted on prenatal ultrasound. The pregnancy was carried to 38 weeks of gestation, and a 2375-g phenotypically normal male baby was delivered. The karyotypes of umbilical cord, cord blood and placenta were 46,XY (40/40 cells), 47,XY,+9[1]/46,XY[39] and 47,XY,+9[12]/46,XY[28], respectively. QF-PCR assays on placenta showed trisomy 9 of maternal origin. When follow-up at age two months, the neonate was normal in development. The peripheral blood had a karyotype of 46,XY (40/40 cells), and the buccal mucosal cells had 7.5% (8/106 cells) mosaicism for trisomy 9 by interphase FISH analysis.ConclusionLow-level mosaic trisomy 9 at amniocentesis can be associated with a favorable fetal outcome and cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes.     

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.     

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.     

Mosaic trisomy 16 at amniocentesis in a pregnancy associated with positive non-invasive prenatal testing for trisomy 16, placental trisomy 16, intrauterine growth restriction,intrauterine fetal death,cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes,and prenatal progressive decrease of the aneuploid cell line

ObjectiveWe present mosaic trisomy 16 at amniocentesis in a pregnancy associated with positive non-invasive prenatal testing (NIPT) for trisomy 16, placental trisomy 16, intrauterine growth restriction (IUGR), intrauterine fetal death (IUFD), cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes and uncultured amniocytes, and prenatal progressive decrease of the aneuploid cell line.Case reportA 26-year-old, primigravid woman underwent amniocentesis at 17 weeks of gestation because of positive NIPT for trisomy 16 at 12 weeks of gestation. Amniocentesis revealed a karyotype of 47,XX,+16 [10]/46,XX[17], and simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed the result of arr (16) × 3 [0.43] consistent with 43% mosaicism for trisomy 16. She was referred for genetic counseling at 19 weeks of gestation, and a fetus with IUGR was noted to have a size equivalent to 16 weeks of gestation. At 23 weeks of gestation, the fetus manifested oligohydramnios, fetal cardiomegaly and severe IUGR (fetal size equivalent to 20 weeks of gestation). Repeat amniocentesis revealed a karyotype of 46,XX (20/20 colonies) in cultured amniocytes and mosaic trisomy 16 by aCGH in uncultured amniocytes. aCGH analysis on uncultured amniocytes revealed the result of arr 16p13.3q24.3 × 2.3, consistent with 30% (log₂ ratio = 0.2) mosaicism for trisomy 16. Quantitative fluorescence polymerase chain reaction (QF-PCR) assays on the DNA extracted from parental bloods and uncultured amniocytes excluded uniparental disomy (UPD) 16. The parental karyotypes were normal. IUFD was noted at amniocentesis. The pregnancy was subsequently terminated, and a 288-g female fetus was delivered with no phenotypic abnormalities. The umbilical cord had a karyotype of 46,XX (40/40 cells), and the placenta had a karyotype of 47,XX,+16 (40/40 cells). QF-PCR assays of the placenta confirmed a maternal origin of trisomy 16.ConclusionMosaic trisomy 16 at amniocentesis can be associated with positive NIPT for trisomy 16, placental trisomy 16, IUGR, IUFD, cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes, and prenatal progressive decrease of the aneuploid cell line.     

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.     

Monozygotic twins discordant for low-level mosaic trisomy 17 at amniocentesis in a pregnancy with a favorable outcome and a literature review of heterokaryotypic monozygotic twins at amniocentesis

ObjectiveWe present a set of twins discordant for low-level mosaic trisomy 17 at amniocentesis, and we review the literature of heterokaryotypic monozygotic twins at amniocentesis.Materials and methodsWe describe a monozygotic twin pregnancy with discordant karyotypes and structural abnormalities. A 22-year-old, primigravid woman underwent amniocentesis at 21 weeks of gestation because of an abnormal maternal serum screening result for Down syndrome. Prenatal ultrasound revealed twin-twin transfusion syndrome but no detectable fetal structural abnormalities. Conventional cytogenetic analysis was applied on cultured amniocytes and parental bloods. Polymorphic DNA marker analysis by quantitative fluorescent polymerase chain reaction (QF-PCR) testing was performed on the DNAs extracted from cultured amniocytes, parental bloods and peripheral bloods of the twins after birth. Interphase fluorescence in situ hybridization (FISH) analysis was performed on buccal mucosal epithelial cells.ResultsAmniocentesis revealed a karyotype of 47,XX,+17 [3]/46,XX [23] in twin A and a karyotype of 46,XX in twin B. The parental karyotypes were normal. QF-PCR confirmed monozygotic twinning and excluded uniparental disomy (UPD) 17. At 35 weeks of gestation, a 1778-g twin A and a 2396-g twin B were delivered smoothly. Both infants had the karyotype of 46,XX in the peripheral bloods and were phenotypically normal except that twin A had preaxial polydactyly on the right hand. Postnatal QF-PCR testing confirmed monozygotic twinning. The infants were doing well at age 2 years and 7 months at follow-ups with normal physical and psychomotor development. FISH analysis on buccal mucosal epithelial cells showed trisomy 17 signals in 4.16% (4/96) cells, compared with 5% (5/101 cells) in normal control.ConclusionsMonozygotic twins discordant for low-level mosaic trisomy 17 at amniocentesis without ultrasound abnormalities can have a favorable outcome. Prenatal diagnosis of twins discordant for structural abnormalities and/or chromosomal aberrations should alert the possibility of monozygotic twinning, and QF-PCR testing is useful for rapid determination of zygosity and exclusion of UPD under such a circumstance.     

Prenatal diagnosis of mosaicism for double aneuploidy of 47,XXY and trisomy 7 (48,XXY,+7) at amniocentesis in a pregnancy with a favorable outcome

ObjectiveWe present prenatal diagnosis of mosaicism for double aneuploidy of 47, XXY and trisomy 7 (48,XXY,+7) at amniocentesis in a pregnancy with a favorable outcome.Case reportA 33-year-old woman underwent amniocentesis at 17 weeks of gestation because of an increased risk for Down syndrome in maternal serum screening. Amniocentesis revealed a karyotype of 48,XXY,+7[8]/46,XY[16]. Simultaneous array comparative genomic hybridization (aCGH) analysis on uncultured amniocytes revealed the result of arr [GRCh37] (7) × 3 [0.54], (X) × 2 [0.52], (Y) × 1, compatible with trisomy 7 mosaicism and Klinefelter syndrome mosaicism. The parental karyotypes and prenatal ultrasound findings were normal. Repeat amniocentesis performed at 23 weeks of gestation revealed a karyotype of 48,XXY,+7[13]/46,XY[7]. Simultaneous molecular cytogenetic analyses on uncultured amniocytes revealed 30% mosaicism for 48,XXY,+7 by aCGH and 37% (37/100 cells) mosaicism for trisomy 7 and disomy X by interphase fluorescence in situ hybridization (FISH) analysis. Polymorphic DNA marker analysis excluded uniparental disomy (UPD) 7 and indicated a maternal origin of the chromosome aberration. The pregnancy was continued to 39 weeks of gestation, and a 3070-g healthy male baby was delivered. The cord blood had a karyotype of 46,XY, the umbilical cord had a karyotype of 48,XXY,+7[3]/46,XY[37], and the placenta had a karyotype of 48,XXY,+7. At age one month, the neonate was phenotypically normal, and interphase FISH analysis revealed 4.8% (5/105 cells) mosaicism on buccal mucosal cells and 8.9% (8/90 cells) mosaicism on urinary cells for trisomy 7 and disomy X, compared with 2% in normal control. Interphase FISH analysis on buccal mucosal cells at age two months revealed normal findings in 100/100 cells.ConclusionMosaic 48,XXY,+7 at amniocentesis without UPD 7 can be associated with a favorable fetal outcome. Cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes may occur in mosaic 48,XXY,+7 at amniocentesis.