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 13 at amniocentesis in a pregnancy associated with a favorable fetal outcome and cytogenetic discrepancy in various tissues

ObjectiveWe present low-level mosaic trisomy 13 at amniocentesis in a pregnancy associated with associated with a favorable fetal outcome and cytogenetic discrepancy in various tissues.Case ReportA 38-year-old, gravida 3, para 0, woman underwent amniocentesis at 19 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,+13[2]/ 46,XX[20] in co-twin A and a karyotype of 46,XY in co-twin B. In co-twin A, among 22 colonies of cultured amniocytes, two colonies had a karyotype of 47,XX,+13, whereas the rest 20 colonies had the karyotype of 46,XX. Array comparative genomic hybridization (aCGH) analysis on the DNA extracted from cultured amniocytes revealed arr (1-22,X) × 2, Y × 0 and detected 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) 13. The woman was encouraged to continue the pregnancy. At 37 weeks of gestation, a normal 2410-g female co-twin A and a normal 2360-g male co-twin B were delivered without any phenotypic abnormality. The karyotypes of cord blood, umbilical cord and placenta of co-twin A were 46,XX (40/40 cells), 47,XX,+13 [1]/46,XX[39] and 47,XX,+13[36]/46,XX [4], respectively. QF-PCR analysis on cord blood of co-twin A excluded UPD 13. When follow-up at age 1½ years, the neonate of co-twin A was normal in physical and psychomotor development.ConclusionLow-level true mosaic trisomy 13 at amniocentesis can be associated with a favorable fetal outcome and cytogenetic discrepancy in various tissues.     

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.     

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.     

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.     

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 trisomy 20 at amniocentesis in a pregnancy with a favorable outcome

ObjectiveWe present our observation of cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes in mosaic trisomy 20 at amniocentesis in a pregnancy with a favorable outcome.Case reportA 35-year-old woman underwent amniocentesis at 16 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 47,XX,+20[10]/46,XX[15]. Among 25 colonies of cultured amniocytes, 10 colonies had a karyotype of 47,XX,+20, while the rest were normal. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed no genomic imbalance, or arr (1–22,X) × 2. The parental karyotypes were normal. Following genetic counseling, the woman underwent repeat amniocentesis at 20 weeks of gestation. Repeat amniocentesis revealed a karyotype of 47,XX,+20[3]/46,XX[35]. Among 38 colonies of cultured amniocytes, three colonies had a karyotype of 47,XX,+20, while the rest were normal. Simultaneous aCGH analysis on the DNA extracted from uncultured amniocytes revealed no genomic imbalance, or arr (1–22,X) × 2. Interphase fluorescence in situ hybridization analysis on 101 uncultured amniocytes detected only one cell with three chromosome 20 signals with a mosaic trisomy 20 level of 1% (1/101 cells), compared with 0% in normal control. Polymorphic DNA marker analysis on the DNA extracted from uncultured amniocytes and parental bloods excluded uniparental disomy 20. At 38 weeks of gestation, a phenotypically normal 3120-g female baby was delivered. Cytogenetic analysis of cord blood, placental tissue and umbilical cord revealed a karyotype of 46,XX. The neonate was normal at postnatal follow-ups. Postnatal interphase fluorescence in situ hybridization analysis on 100 buccal mucosal cells revealed no trisomy 20 signals.ConclusionMosaic trisomy 20 at amniocentesis can be a cultured artifact. Complete cytogenetic discrepancy may occur between cultured amniocytes and uncultured amniocytes in mosaic trisomy 20 at amniocentesis, and molecular cytogenetic analysis on uncultured amniocytes is useful for rapid distinguishing true mosaicism from pseudomosaicism under such as circumstance.     

Mosaic tetrasomy 9p at amniocentesis in a pregnancy associated with a favorable fetal outcome,perinatal progressive decrease of the aneuploid cell line and cytogenetic discrepancy in various tissues

ObjectiveWe present mosaic tetrasomy 9p at amniocentesis in a pregnancy associated with a favorable fetal outcome, perinatal progressive decrease of the aneuploid cell line and cytogenetic discrepancy in various tissue.Case reportA 33-year-old primigravid woman underwent elective amniocentesis at 18 weeks of gestation because of anxiety, and the karyotype of cultured amniocytes was 47,XX,+i (9) (p10)[20]/46,XX [55]. Cordocentesis was performed at 20 weeks of gestation, and the karyotype of cord blood was 47,XX,+i (9) (p10)[7]/46,XX [15]. She was referred for genetic counseling at 23 weeks of gestation, and repeat amniocentesis revealed a karyotype of 47,XX,+i (9) (p10)[1]/46,XX [16] with seven cells in one colony having tetrasomy 9p in cultured amniocytes, and in uncultured amniocytes, quantitative fluorescence polymerase chain reaction (QF-PCR) analysis excluded uniparental disomy (UPD) 9 and determined paternal origin of the extra i (9p), array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed arr 9p24.3p13.1 × 3.0 consistent with 50% mosaicism for tetrasomy 9p, and interphase fluorescence in situ hybridization (FISH) on uncultured amniocytes showed 22.6% (12/53 cells) mosaicism for tetrasomy 9p. A third amniocentesis at 27 weeks of gestation revealed a karyotype of 46, XX (10/10 colonies) in cultured amniocytes, and interphase FISH analysis on uncultured amniocytes revealed 20% (20/100 cells) mosaicism for tetrasomy 9p. The parental karyotypes and prenatal ultrasound were normal. At 39 weeks of gestation, a phenotypically normal 3388-g female baby was delivered. The karyotypes of cord blood, umbilical cord and placenta were 47,XX,+idic (9) (q12)[19]/46,XX [21] or 47,XX,+idic (9) (pter→q12:q12→pter)[19]/46,XX [21], 47,XX,+idic (9) (q12)[1]/46,XX [39] and 47,XX,+idic (9) (q12)[4]/46,XX [36], respectively. When follow-up at age two months, the neonate was phenotypically normal, the peripheral blood had a karyotype of 47,XX,+idic (9) (q12)[18]/46,XX [22], and interphase FISH analysis on 100 buccal mucosal cells revealed 1% (1/100 cells) mosaicism for tetrasomy 9p. When follow-up at age seven months, the neonate was phenotypically normal, and the peripheral blood had a karyotype of 47,XX,+idic(9)(q12)[14]/46,XX[26].ConclusionMosaic tetrasomy 9p at amniocentesis can be a transient and benign condition, and can be associated with a favorable fetal outcome and perinatal progressive decrease of the aneuploid cell line and cytogenetic discrepancy in various tissue.     

Low-level mosaic trisomy 13 at amniocentesis associated with a favorable outcome in a pregnancy

ObjectiveWe present low-level mosaic trisomy 13 at amniocentesis associated with a favorable outcome in a pregnancy.Case reportA 39-year-old woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 47,XY,+13[8]/46,XY[20]. The woman underwent cord blood sampling at 22 weeks of gestation. Cytogenetic analysis of cord blood revealed a karyotype of 47,XY,+13[2]/46,XY[98]. Array comparative genomic hybridization (aCGH) analysis on the DNA extracted from cord blood revealed 10% gene dosage increase in chromosome 13. Prenatal ultrasound findings were unremarkable. After genetic counseling, the parents decided to continue the pregnancy, and a 2,280-g healthy male baby was delivered at 38 weeks of gestation. The parental karyotypes were normal. The cord blood at birth had a karyotype of 47,XY,+13[1]/46,XY[49]. At age one month, interphase fluorescence in situ hybridization (FISH) analysis revealed no trisomy 13 signals in 100/100 buccal mucosal cells, and trisomy 13 signals in 2/54 (3.7%) urinary cells compared with 0/60 cells in the normal control. The neonate was doing well and presented neither phenotypic abnormalities nor psychomotor disorders at age two months.ConclusionLow-level true mosaic trisomy 13 at amniocentesis without ultrasound abnormalities can be associated with a favorable outcome.     

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 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.     

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.     

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.     

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.     

Mosaic 46,XY,dup(14) (q12q22.3)/46, XY at amniocentesis in a pregnancy associated with a favorable fetal outcome and cytogenetic discrepancy in various tissues

ObjectiveWe present mosaic 46,XY,dup (14) (q12q22.3)/46, XY at amniocentesis in a pregnancy associated with a favorable fetal outcome and cytogenetic discrepancy in various tissues.Case reportA 41-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. Cytogenetic analysis on cultured amniocytes revealed a karyotype of 46,XY, dup (14) (q12q22.3)[7]/46,XY [13], and simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed arr 14q12q22.3 × 2–3 with 25% mosaicism for partial 14q duplication. She was referred for genetic counseling. Prenatal ultrasound and parental karyotypes were normal. Repeat amniocentesis at 22 weeks of gestation revealed a karyotype of 46,XY,dup (14) (q12q22.3)[6]/46,XY [14], and in uncultured amniocytes, quantitative fluorescence polymerase chain reaction (QF-PCR) analysis excluded uniparental disomy (UPD) 14, aCGH revealed arr 14q12q22.3 × 2.3 with 30% mosaicism for dup (14) (q12q22.3), and interphase fluorescence in situ hybridization (FISH) showed 19.4% (24/124 cells) mosaicism for partial 14q duplication. She was encouraged to continue the pregnancy, and a 2450-g phenotypically normal male baby was delivered at 40 weeks of gestation. The karyotypes of cord blood, umbilical cord and placenta were 46,XY,dup (14) (q12q22.3)[14]/46,XY [26], 46,XY,dup (14) (q12q22.3)[7]/46,XY [33] and 46,XY,dup (14) (q12q22.3)[3]/46,XY [37], respectively. When follow-up at age four months, the neonate was phenotypically normal. The karyotype of peripheral blood was 46,XY,dup (14) (q12q22.3)[27]/46,XY [13], and interphase FISH analysis on 105 buccal mucosal cells detected partial 14q duplication signals in 5 cells (4.8% mosaicism). When follow-up at age nine months, the neonate was phenotypically normal. The karyotype of peripheral blood was 46,XY,dup (14) (q12q22.3)[25]/46,XY [15].ConclusionMosaic dup (14) (q12q22.3) with a normal cell line at amniocentesis may be a benign condition, and can be associated with a favorable fetal outcome and cytogenetic discrepancy in various tissues.     

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.     

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 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.     

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.