Search

Objective: We present low-level mosaic trisomy 21 at amniocentesis in a pregnancy with a favorable fetal outcome. Case report: A 34-year-old, primigravid woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 47,XY,+21 [7]/46,XY [33]. At 23 weeks of gestation, repeat amniocentesis revealed a karyotype of 47,XY,+21 [4]/46,XY [22], and cord blood sampling revealed the karyotype of 47,XY,+21 [5]/46,XY [35]. The parental karyotypes were normal. Quantitative fluorescent polymerase chain reaction (QF-PCR) analysis on uncultured amniocytes and parental bloods excluded UPD 21, array comparative genomic hybridization (aCGH) analysis on uncultured amniocytes revealed the result of arr 21q11.2q22.3 × 2.3, consistent with 30% mosaicism for trisomy 21. Interphase fluorescence in situ hybridization (FISH) analysis on uncultured amniocytes revealed 43.8% (35/80 cells) mosaicism for trisomy 21. The woman was advised to continue the pregnancy, and a phenotypically normal 3,340-g male baby was delivered at 39 weeks of gestation. The cord blood had a karyotypes of 46,XY (40/40 cells). QF-PCR on placenta showed mosaic trisomy 21. When follow-up at age three months, the neonate was normal in phenotype and development. FISH analysis on buccal mucosal cells showed 9% (10/101 cells) mosaicism for trisomy 21, compared with 0% (0/100 cells) in the normal control. Conclusion: Low-level mosaic trisomy 21 at amniocentesis can be associated with cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes, perinatal progressive decrease of the aneuploid cell line and a favorable fetal outcome.

Objective: We present high-level mosaicism for 45,X in 45,X/46,X,+mar at amniocentesis in a pregnancy associated with positive non-invasive prenatal testing (NIPT) for Turner syndrome, normal male external genitalia and positive SRY in the fetus, a favorable fetal outcome, postnatal decrease of the 45,X cell line and cytogenetic discrepancy in various tissues. Case report: A 35-year-old, gravida 2, para 1, woman underwent amniocentesis at 16 weeks of gestation because of positive NIPT for Turner syndrome (Z score = −11.72 for X chromosome) at 10 weeks of gestation. Amniocentesis revealed a karyotype of 45,X[13]/46,X,+mar[8]. Simultaneous molecular analysis on the DNA extracted from uncultured amniocytes revealed the results of arr (X) × 1, (Yp) × 0–1 (0.63), (Yq) × 0, (1–22) × 2 in array comparative genomic hybridization (aCGH) and rsa(X) × 1, Yp11.31 × 0–1, Yq11.21 × 0, (13, 18, 21) × 2 in multiplex ligation-dependent probe amplification (MLPA). The parental karyotypes were normal. Prenatal ultrasound revealed normal male external genitalia. She was referred for genetic counseling, and continuing pregnancy was advised. A 2875-g male baby was delivered at 38 weeks of gestation with normal male external genitalia. The karyotypes of cord blood, umbilical cord and placenta were 46,X,+mar[27]/45,X[13], 46,X,+mar[24]/45,X[16] and 45,X[22]/46,X,+mar[18], respectively. SRY testing on cord blood revealed a positive result. When follow-up at age two months, the neonate was normal in development. The karyotype of peripheral blood was 46,X,+mar[25]/45,X[13]/46,X,idic r(Y) [2]. Interphase fluorescence in situ hybridization (FISH) analysis on 103 buccal mucosal cells using Yp11.2-specific probe RP11-119E4 and Xp22.31-specific probe RP11-143E20 showed that 90 cells (90/103 = 87%) had double Yp signals, 3 cells (3/103 = 3%) had single Yp signal and 10 cells (10/103 = 10%) had no Yp signal. Conclusion: High-level mosaicism for 45,X in 45,X/46,X,+mar at amniocentesis with positive Yp and SRY can be associated with a favorable fetal outcome, postnatal decrease of the 45,X cell line and cytogenetic discrepancy in various tissues.

Objective: We present low-level mosaic trisomy 2 at amniocentesis in a pregnancy associated with positive non-invasive prenatal testing (NIPT) and chorionic villus sampling (CVS) results for trisomy 2, maternal uniparental disomy (UPD) 2, perinatal progressive decrease of the aneuploid cell line, cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes, intrauterine growth restriction (IUGR) and a favorable fetal outcome. Case Report: A 35-year-old, primigravid woman underwent amniocentesis at 16 weeks of gestation because both NIPT at 9 weeks of gestation and CVS at 11 weeks of gestation revealed trisomy 2. This pregnancy was conceived by in vitro fertilization (IVF) and embryo transfer (ET). Amniocentesis revealed a karyotype of 47,XY,+2[11]/46,XY[19]. Prenatal ultrasound findings were normal. She was referred to the hospital for genetic counseling at 20 weeks of gestation, and repeat amniocentesis performed at 24 weeks of gestation revealed a karyotype of 46,XY (22/22 colonies). The parental karyotypes were normal. Quantitative fluorescent polymerase chain reaction (QF-PCR) analysis on the DNA extracted from uncultured amniocytes and parental bloods revealed maternal uniparental heterodisomy of chromosome 2. Simultaneous molecular cytogenetic analysis on uncultured amniocytes showed the results of arr 2p25.3q37.3 × 2.4 with a log2 ratio = 0.26, consistent with 40% mosaicism for trisomy 2 by array comparative genomic hybridization (aCGH), and 28% (28/100 cells) mosaicism for trisomy 2 by interphase fluorescence in situ hybridization (FISH). Despite IUGR on fetal ultrasound, the woman was advised to continue the pregnancy, and a 2252-g phenotypically normal male baby was delivered at 38 weeks of gestation. The karyotypes of cord blood, umbilical cord and placenta were 46,XY (40/40 colonies), 46,XY (40/40 colonies) and 47,XY,+2[9]/46,XY[31], respectively. QF-PCR analysis on cord blood, umbilical cord and placenta confirmed uniparental heterodisomy of chromosome 2 in the cord blood and umbilical cord, and maternal origin of trisomy 2 in the placenta. FISH analysis on buccal mucosal cells at age 1.5 months revealed 8.7% (9/104 cells) mosaicism for trisomy 2. When follow-up at age four months, the neonate manifested a normal phenotype except intermittent hypoventilation. Molecular analysis of the PHOX2B gene revealed a normal result. When follow-up at age one year, he manifested normal development. Conclusion: Mosaic trisomy 2 at prenatal diagnosis should alert the possibility of UPD 2 and include a UPD 2 testing. Low-level mosaic trisomy 2 at amniocentesis can be associated with perinatal progressive decrease of the aneuploid cell line and a favorable fetal outcome.

Objective: We present low-level mosaic trisomy 13 at amniocentesis in a pregnancy associated with a positive non-invasive prenatal testing (NIPT) result suspicious of trisomy 13, a chorionic villus sampling (CVS) result of mosaic trisomy 13, cytogenetic discrepancy in various tissues and a favorable fetal outcome. Case report: A 29-year-old, gravida 2, para 1, woman underwent amniocentesis at 20 weeks of gestation because of a positive NIPT result (Z-score = 20.9, positive ≥3) suspicious of trisomy 13 at 11 weeks of gestation and a CVS result of mosaic trisomy 13 at 14 weeks of gestation. At 14 weeks of gestation, CVS revealed the multiplex ligation-dependent probe amplification (MLPA) result of rea X,Y (P095) × 1, 13 (P095) × 3, 18,21 (P095) × 2/X,Y (P095) × 1, 13,18,21 (P095) × 2 and a karyotype of 48,XY,+13,+mar [9]/47,XY,+mar[16]. She was referred to the hospital for genetic counseling at 15 weeks of gestation, and cytogenetic analysis of parental blood revealed 47,XY,+mar in the father and 46, XX in the mother. Fluorescence in situ hybridization (FISH) analysis on the paternal blood showed that the extra dicentric marker was derived from chromosome 15 without the locus SNRPN (15q11.2), and the result was 47,XY,+mar.ish dic(15) (D15Z1++, SNRPN-, PML-)[20]. Amniocentesis at 20 weeks of gestation revealed a karyotype of 47,XY,+mar pat (20/20). Simultaneous interphase FISH analysis on uncultured amniocytes revealed 32% (32/100 cells) mosaicism for trisomy 13. Quantitative fluorescence polymerase chain reaction (QF-PCR) analysis using the DNA extracted from the parental bloods and uncultured amniocytes excluded uniparental disomy (UPD) 13. Prenatal ultrasound findings were normal. The woman was advised to continue the pregnancy, and a phenotypically normal 2708-g male baby was delivered at 38 weeks of gestation, The cord blood, umbilical cord and placenta had the karyotypes of 47,XY,+mar pat and did not have UPD 13. When follow-up at age two months, the neonate was phenotypically normal. FISH analysis on buccal mucosal cells detected 5.3% (5/95 cells) mosaicism for trisomy 13, compared with 0% in the normal control. Conclusion: Low-level mosaic trisomy 13 at amniocentesis can be associated with a positive NIPT result suspicious of trisomy 13, a CVS result of mosaic trisomy 13, cytogenetic discrepancy in various tissues and a favorable fetal outcome.

Objective: We 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 report: A 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. Conclusion: Mosaic 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.

Objective: We 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 report: A 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. Conclusion: Low-level mosaic trisomy 9 at amniocentesis can be associated with a favorable fetal outcome and cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes.

Objective: We 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 report: A 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. Conclusion: Mosaic 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.

Objective: We present molecular cytogenetic characterization of del(X) (p22.33)mat and de novo dup(4) (q34.3q35.2) in a male fetus with multiple anomalies of facial dysmorphism, ventriculomegaly, congenital heart defects, short long bones and clinodactyly. Case report: A 36-year-old, gravida 3, para 1, woman with short stature (152 cm) underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 46,Y,del(X)(p22.33)mat, dup(4)(q34.3q35.2). The mother had a karyotype of 46,X,del(X)(p22.33). Array comparative genomic hybridization (aCGH) analysis on the DNA extracted from cultured amniocytes revealed arr Xp22.33 × 0, 4q34.3q35.2 × 3. Prenatal ultrasound at 23 weeks of gestation revealed multiple anomalies of flat nasal bridge, ventriculomegaly, atrioventricular septal defect (AVSD) and clinodactyly. The pregnancy was subsequently terminated, and a malformed fetus was delivered with facial dysmorphism. Cytogenetic analysis of the umbilical cord revealed 46,Y,del(X)(p22.33)mat, dup(4)(q34.3q35.2)dn. aCGH analysis on the DNA extracted from the umbilical cord revealed arr [GRCh37 (hg19)] 4q34.3q35.2 (181,149,823–188,191,938) × 3.0, arr Xp22.33 (470,485–2,985,006) × 0 with a 7.042-Mb duplication of 4q34.3-q35.2 and a 2.514-Mb deletion of Xp22.33. Conclusion: A male fetus with del(X)(p22.33) and dup(4)(q34.3q35.2) may present congenital heart defects and short long bones on prenatal ultrasound.

Objective: We present mosaic trisomy 21 at amniocentesis associated with a favorable fetal outcome and perinatal progressive decrease of the trisomy 21 cell line. Case report: A 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]. Conclusion: Mosaic trisomy 21 at amniocentesis can be a transient and benign condition, and the abnormal trisomy 21 cell line may decrease and disappear after birth.

Objective: We 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 report: A 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]. Conclusion: Mosaic 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.

Objective: We present prenatal diagnosis and molecular cytogenetic characterization of a de novo duplication of 2q12.2→q13 encompassing MALL, NPHP1, RGPD6 and BUB1. Case report: A 36-year-old, primigravid woman underwent amniocentesis at 16 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 46,XX,dup(2) (q12.2q13). Simultaneous array comparative genomic hybridization (aCGH) analysis revealed a 6.1-Mb 2q12.2q13 duplication. aCGH analysis of the parental bloods did not find such a duplication. Prenatal ultrasound was unremarkable. After genetic counseling, the parents decided to terminate the pregnancy at 21 weeks of gestation, and a 420-g female fetus was delivered with no gross abnormalities. Postnatal cytogenetic analysis of the umbilical cord confirmed the prenatal diagnosis. The parental karyotypes were normal. aCGH analysis of the umbilical cord revealed the result of arr [GRCh37 (hg19)] 2q12.2q13 (107, 132, 950–113,065,779) × 3.0 with a 2q12.2→q13 duplication encompassing 20 OMIM genes including MALL, NPHP1, RGPD6 and BUB1. Polymorphic DNA marker analysis of quantitative fluorescence polymerase chain reaction (QF-PCR) on the DNAs extracted from the umbilical cord and parental bloods confirmed a maternal origin of the duplication of 2q12.2→q13. Conclusion: Amniocentesis may incidentally detect a de novo chromosomal segmental duplication of maternal origin in the fetus. The genetic information acquired by molecular analyses such as aCGH and QF-PCR are useful for genetic counseling under such a circumstance.

Objective: We present mosaic 45,X/46, XX at amniocentesis with high-level mosaicism for 45,X in a pregnancy with a favorable fetal outcome and postnatal decrease of the 45,X cell line. Case report: A 20-year-old, primigravid woman underwent amniocentesis at 17 weeks of gestation because of the non-invasive prenatal testing (NIPT) result of −4.82 Z score in sex chromosome at 12 weeks of gestation suggestive of Turner syndrome in the fetus. Amniocentesis revealed a karyotype of 45,X [18]/46,XX [15], and simultaneous multiplex ligation-dependent probe amplification (MLPA) on the DNA extracted from uncultured amniocytes showed mosaic Turner syndrome. Prenatal ultrasound and parental karyotypes were normal. She was referred for genetic counseling at 24 weeks of gestation, and continuing pregnancy was encouraged. At 39 weeks of gestation, a 2550-g phenotypically normal female baby was delivered. The karyotypes of cord blood, umbilical cord and placenta were 45,X [24]/46,XX [16], 45,X [23]/46,XX [17] and 45,X [28]/46,X,del(X) (q23)[12], respectively. When follow-up at age two months, the neonate was phenotypically normal in development. The peripheral blood had a karyotypes of 45,X [16]/46,XX [24]. Interphase fluorescence in situ hybridization (FISH) analysis on 103 buccal mucosal cells showed normal disomy X signals in all cells. Conclusion: High-level mosaicism for 45,X in 45,X/46, XX at amniocentesis can be associated with a favorable fetal outcome, cytogenetic discrepancy in various tissues, and postnatal decrease of the 45,X cell line.

Objective: We 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 report: A 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. Conclusion: Low-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.

Objective: We present prenatal diagnosis of high-level mosaicism for 45,X by amniocentesis in a pregnancy with a favorable fetal outcome. Case report: A 35-year-old, gravida 2, para 1, woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 45,X[13]/46,XY[11]. Simultaneous array comparative genomic hybridization (aCGH) on uncultured amniocytes revealed the result of Yp11.3q11.21 × 0–1 [0.1], Yq11.21q11.23 × 0–1 [0.6]. At 19 weeks of gestation, she underwent the second amniocentesis which revealed a karyotype of 45,X[13]/46,XY[12], and aCGH and multiplex ligation-dependent probe amplification (MLPA) on uncultured amniocytes showed 37% mosaicism for Y-deleted cells. At 28 weeks of gestation, she underwent the third amniocentesis which revealed a karyotype of 45,X[25]/46,XY[25], and aCGH on uncultured amniocytes revealed the result of Yq11.21q11.23 × 0.5, Yq11.23q12 × 0.7. Interphase fluorescence in situ hybridization (FISH) analysis on uncultured amniocytes revealed that 16.67% (20/120 cells) were Y-deleted cells. The parental karyortypes and prenatal ultrasound were normal. At 37 weeks of gestation, a 2707-g phenotypically normal male baby was delivered with normal male external genitalia. The karyotypes of cord blood, umbilical cord and placenta were 45,X[25]/46,XY[15], 45,X[18]/46,XY[22] and 45,X[25]/46,XY[15], respectively. When follow-up at age five months, the neonate was normal in external genitalia and physical development. The peripheral blood had a karyotype of 45,X[29]/46,XY[11], and FISH analysis on 100 buccal mucosal cells showed no abnormal signals. When follow-up at age 11 months, the neonate was physically normal, and the peripheral blood had a karyotype of 45,X[17]/46,XY[23]. Conclusion: High-level mosaicism for 45,X in 45,X/46, XY at amniocentesis can be associated with a favorable fetal outcome despite the presence of cytogenetic discrepancy in various tissues.

Objective: We present prenatal diagnosis of mosaic trisomy 18 in a pregnancy with a favorable fetal outcome and maternal uniparental disomy 18. Case report: A 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. Conclusion: Cytogenetic 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.

Objective: We present prenatal diagnosis of mosaic trisomy 18 by amniocentesis associated with a favorable fetal outcome in a pregnancy. Case report: A 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]. Conclusions: Mosaic 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.

Objective: We present prenatal diagnosis of mosaic trisomy 16 by amniocentesis in a pregnancy associated with an abnormal first-trimester screening result, intrauterine growth restriction (IUGR) and a favorable outcome. Case report: A 27-year-old woman underwent amniocentesis at 18 weeks of gestation because of an abnormal first-trimester screening result with maternal serum free β-hCG of 1.474 multiples of the median (MoM), pregnancy associated plasma protein-A (PAPP-A) of 0.122 MoM and placental growth factor (PlGF) of 0.101 MoM, and a Down syndrome risk of 1/45. Amniocentesis revealed a karyotype of 47,XY,+16 [9]/46,XY [16] and an abnormal array comparative genomic hybridization (aCGH) result of arr (16) × 3 [0.54] compatible with 54% mosaicism for trisomy 16 in uncultured amniocytes. At 24 weeks of gestation, repeat amniocentesis revealed a karyotype of 47,XY,+16 [4]/46,XY [16] and an aCGH result of arr 16p13.3q24.3 (96,766–90,567,357) × 2.25 with a log2 ratio = 0.2 compatible with 20–30% mosaicism for trisomy 16 in uncultured amniocytes. Quantitative fluorescent polymerase chain reaction (QF-PCR) excluded uniparental disomy (UPD) 16. Interphase fluorescence in situ hybridization (FISH) analysis on uncultured amniocytes revealed 19.4% (12/62 cells) mosaic trisomy 16. Prenatal ultrasound revealed IUGR. At 36 weeks of gestation, a phenotypically normal baby was delivered with a body weight of 1900 g. The cord blood had a karyotype of 46,XY. QF-PCR analysis confirmed biparentally inherited disomy 16 in the cord blood and maternal-origin of trisomy 16 in the placenta. When follow-up at age two months, FISH analysis on 101 buccal mucosal cells and 32 urinary cells revealed no signal of trisomy 16. Conclusion: Mosaic trisomy 16 at amniocentesis can be associated with IUGR and an abnormal first-trimester screening result with low PAPP-A and low PlGF. Mosaic trisomy 16 without UPD 16 at amniocentesis can have a favorable outcome, and the abnormal triosmy 16 cell line may disappear after birth.

Objective: We 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 report: A 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. Conclusion: Mosaic 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.

Objective: We present prenatal diagnosis of a 15q11.2-q14 deletion of paternal origin associated with increased nuchal translucency (NT), mosaicism for de novo multiple unbalanced translocations involving 15q11-q14, 5qter, 15qter, 17pter and 3qter, and Prader–Willi syndrome (PWS). Case report: A 32-year-old, primigravid woman underwent amniocentesis at 18 weeks of gestation because of an increased NT thickness of 5.6 mm and abnormal maternal serum screening results in the first trimester. The pregnancy was conceived by in vitro fertilization and embryo transfer. Amniocentesis revealed a karyotype of 45,XX,der(5)t(5;15)(q35;q14),-15 [16]/45,XX,-15,der(17)t(15;17)(q14;p13)[3]/45,XX,der(15)t(15;15)(q35;q14),-15[2]. The parental karyotypes were normal. Prenatal ultrasound findings were unremarkable. Array comparative genomic hybridization (aCGH) analysis on the DNA extracted from cultured amniocytes revealed the result of arr 15q11.2q14 (22,765,628–38,651,755) × 1.0 [GRCh37 (hg19)] with a 15.886-Mb 15q11.2-q14 deletion encompassing TUBGCP5, CYFIP1, NIPA2, NIPA1, SNRPN, SNURF, SNORD116-1, IPW, UBE3A, ACTC1 and MEIS2. The pregnancy was subsequently terminated, and a malformed fetus with facial dysmorphism was delivered. The cord blood had a karyotype of 45,XX,der(5)t(5;15)(q35;q14),-15[46]/45,XX,der(3)t(3;15) (q29;q14),-15[2]/45,XX,-15,der(17)t(15;17)(q14;p13)[2]. The placenta had a karyotype of 45,XX,der(5) t(5;15)(q35;q14),-15. Polymorphic DNA marker analysis confirmed a paternal origin of the proximal 15q deletion. Conclusion: Increased NT and abnormal maternal serum screening results may prenatally be associated with PWS. Chromosome 15 rearrangements in PWS include mosaicism for de novo multiple unbalanced translocations.

Objective: We present mosaic trisomy 15 at amniocentesis. Materials and methods: A 41-year-old woman underwent amniocentesis at 16 weeks of gestation because of an abnormal non-invasive prenatal testing (NIPT) result suspicious of trisomy 15. Amniocentesis revealed a karyotype of 46,XY. Array comparative genomic hybridization (aCGH) on uncultured amniocytes revealed 26% mosaicism for trisomy 15. She was referred for repeat amniocentesis. aCGH, interphase fluorescence in situ hybridization (FISH), quantitative fluorescent polymerase chain reaction (QF-PCR) assays and/or conventional cytogenetic analysis were applied on various cells and tissues including uncultured amniocytes, cultured amniocytes, cord blood, placenta, parental bloods and/or buccal mucosal cells. Results: Repeat amniocentesis at 21 weeks of gestation revealed a karyotype of 46, XY in cultured amniocytes, and 30% mosaicism for trisomy 15 by aCGH and 32% mosaicism for trisomy 15 by FISH in uncultured amniocytes. Repeat amniocentesis at 29 weeks of gestation revealed a karyotype of 46, XY in cultured amniocytes, and 15% mosaicism for trisomy 15 by aCGH and 7.2% mosaicism for trisomy 15 by FISH in uncultured amniocytes. QF-PCR on cultured amniocytes excluded uniparental disomy (UPD) 15. A phenotypically normal baby was delivered subsequently with a karyotype of 46, XY in cord blood and 2% mosaicism for trisomy 15 by FISH in buccal mucosal cells. The aCGH analysis revealed trisomy 15 in placenta and no genomic imbalance in cord blood. QF-PCR assays determined a maternal origin of trisomy 15 in placenta. Conclusion: Cytogenetic discrepancy may occur between uncultured and cultured amniocytes in mosaic trisomy 15 at amniocentesis. The cells of trisomy 15 cell line in prenatally detected mosaic trisomy 15 may decrease in number as the fetus grows. Whenever NIPT suspects trisomy 15, a confirmatory amniocentesis should include genetic analysis on both uncultured and cultured amniocytes to exclude mosaic trisomy 15 and maternal UPD 15, especially when the cultured amniocytes have a normal karyotype.

Objective: We present perinatal molecular cytogenetic analysis of low-level mosaicism for trisomy 21 in a pregnancy with maternal uniparental disomy (UPD) of chromosome 21 in the fetus. Case report: A 39-year-old woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 47,XX,+21[6]/46,XX[25]. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed arr (21) × 2–3, (X) × 2 with about 18% gene dosage increase in chromosome 21 consistent with mosaic trisomy 21. Cordocentesis was performed at 20 weeks of gestation, and the cord blood lymphocytes had a karyotype of 47,XX,+21[3]/46,XX[72]. Prenatal ultrasound findings were unremarkable. After genetic counseling, the parents decided to continue the pregnancy. At 39 weeks of gestation, a 3,494-g phenotypically normal female baby was delivered without phenotypic features of Down syndrome. There was no dysplasia of middle phalanx of the fifth fingers of both hands. The cord blood had a karyotype of 47,XX,+21[2]/46,XX[48]. The placenta had a karyotype of 47,XX,+21[37]/46,XX[3]. The umbilical cord had a karyotype of 47,XX,+21[1]/46,XX[39]. aCGH analysis on the DNA extracted from cord blood revealed no genomic imbalance. Polymorphic DNA marker analysis on the DNAs extracted from cord blood and parental bloods revealed maternal uniparental heterodisomy 21 in the baby. Interphase fluorescence in situ hybridization analysis on buccal mucosal cells revealed trisomy 21 signals in 15/101 (14.9%) buccal cells at birth and in 1/122 (0.82%) buccal cells at age 45 days. Conclusion: Low-level mosaicism for trisomy 21 at amniocentesis associated with maternal UPD 21 in the fetus can have a favorable outcome.

Objective: We present prenatal diagnosis and molecular cytogenetic characterization of an inverted duplication of proximal chromosome 15 [inv dup(15)] presenting as a small supernumerary marker chromosome (sSMC) at amniocentesis associated with concomitant microduplication of 8q22.1. Materials and methods: A 39-year-old woman underwent amniocentesis at 16 weeks of gestation because of advanced maternal age, and the result was 47, XY, +mar dn. The woman requested for repeat amniocentesis at 20 weeks of gestation. Array comparative genomic hybridization (aCGH), fluorescence in situ hybridization (FISH), quantitative fluorescent polymerase chain reaction (QF-PCR) and DNA methylation analysis were applied to determine the nature of the sSMC.Results: aCGH on the uncultured amniocytes revealed the result of arr 8q22.1 (93,918,763–96,618,539) × 3.0, arr 15q11.2q13.2 (22,765,628–30,658,876) × 4.0, arr 15q13.2q13.3 (30,653,877–32,509,926) × 3.0 [GRCh37 (hg19)]. Interphase FISH analysis using RP11-34H12 [15q13.2; Texas Red, 30,709,033–30,893,021 (hg19)] on 100 uncultured amniocytes showed that 38 cells had three signals, 45 cells had four signals and 27 cells had two signals. The parental bloods had normal aCGH results. The karyotype of cultured amniocytes was 47, XY, +inv dup(15) (pter→q13::q13→pter) which was confirmed by metaphase FISH analysis. No informative markers could be found in QF-PCR analysis. DNA methylation analysis on cord blood confirmed a maternal origin of the 15q11-q13 gene dosage increase with a result of 15q11.2 SNRPN DNA hypermethylation. Postnatal cytogenetic analysis on cord blood, umbilical cord and placenta showed the results consistent with the prenatal diagnosis. Conclusion: Molecular cytogenetic techniques are useful for rapid diagnosis of an inv dup(15) chromosome presenting as an sSMC at amniocentesis.

Objective: We 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 report: A 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. Conclusion: NIPT is useful for rapid differential diagnosis of pseudomosaicism from true mosaicism in case of mosaic trisomy 20 at amniocentesis.

Objective: We 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 report: A 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. Conclusion: Prenatal diagnosis of CPM for trisomy 5 at CVS can be associated with UPD 5 in the fetus, and UPD 5 causes no specific phenotype.

Objective: We present prenatal diagnosis and molecular cytogenetic characterization of a small supernumerary marker chromosome (sSMC) derived from chromosome 3. Case report: A 36-year-old woman underwent amniocentesis at 19 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 47,XX,+mar[6]/46,XX[18]. The mother's karyotype was 47,XX,+mar[4]/46,XX[46]. The father's karyotype was 46.XY. Array comparative genomic hybridization (aCGH) analysis of uncultured amniocytes revealed a result of arr 3q11.1q12.1 (93,575,285–98,956,687) × 2–3 [GRCh37 (hg19)]. Prenatal ultrasound findings were unremarkable. The parents elected to continue the pregnancy, and a 2470-g female baby was delivered at 37 weeks of gestation without phenotypic abnormalities. The cord blood had a karyotype of 47,XX,+mar[8]/46,XX[32]. aCGH analysis of cord blood revealed a result of arr 3q11.1q11.2 (93,649,973–97,137,764) × 2.4 [GRCh37 (hg19)] with a log2 ratio of 0.25 and a 30–40% mosaicism for 3.488-Mb dosage increase in 3q11.1-q11.2 encompassing four [Online Mendelian Inheritance in Man (OMIM)] genes of PROS1, ARL13B, NSUN3 and EPHA6. Metaphase fluorescence in situ hybridization (FISH) analysis confirmed 30% (6/20 cells) mosaicism for the sSMC(3) in the blood lymphocytes. Conclusion: aCGH and FISH analyses are useful for perinatal investigation of a prenatally detected sSMC. Keywords: aCGH, Chromosome 3, FISH, Prenatal diagnosis, Small supernumerary marker chromosome

Objective: We present prenatal diagnosis of a familial 9p12 amplification inherited from a father carrier. Case report: A 38-year-old, gravida 3, para 2, woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a heteromorphic variant of chromosome 9 with a 9p12 amplification on G-band preparations, but it was negative on C-band preparations. Cytogenetic analysis of the parents revealed that the phenotypically normal father carried the same euchromatic 9p + polymorphism. Array comparative genomic hybridization analysis on the DNA extracted from the father's blood revealed no genomic imbalance. At 37 weeks of gestation, a healthy 2760-g female baby was delivered with no phenotypic abnormality. She was doing well at age one year during follow-up. Conclusion: Prenatal diagnosis of a 9p + variant can be a euchromatic chromosome variant of a familial 9p12 amplification without phenotypic consequences.

Objective: To present the calculated frequencies, male to female sex-ratio, and modes of ascertainments in different levels of chromosomal mosaicism (CM) detected at amniocentesis. Materials and methods: This's a 10-years retrospective study between January 2008 and December 2017 and there were 13,752 cases of amniocentesis performed in MacKay Memorial Hospital, Taipei, Taiwan. Eight hundred and thirty four cases of CM were collected in this study. We reviewed their types of chromosomal abnormalities of mosaicism, the modes of ascertainment (including: advanced maternal age, abnormal ultrasound findings, abnormal maternal serum screening result, and other reasons), maternal age, gestational age at amniocentesis, fetal gender, and perinatal findings. After amniocentesis, in situ culture was performed and the results of karyotype with CM were divided in to three levels. Results: In our sample of 13,752 amniocentesis, 834 cases with all levels of CM were collected in this study. Of them, there were 562 cases (4.09%) with level I mosaicism, 207 cases (1.51%) of level II mosaicism, and 65 cases (0.47%) of level III mosaicism (Table 1). In the group of advanced of maternal age (AMA), their calculated frequencies, 4.18% in level I, 1.46% in level II and 0.41% in level III, were very similar to those in total cases (p value = 0.206) without statistical significance. In the group of abnormal ultrasound findings, the calculated frequency was much higher in level III (0.87%), however, there was no statistical significance because of the small numbers of level III. In our cases of amniocentesis, the case numbers of male case (50.20%) is very similar to female (49.80%), and the male to female ratio was 1.01. But, we found more cases of male with CM (444 cases) than female (390 cases). The sex-ratio in different levels’ calculated frequencies of CM showed similar in level I, and male prevalence was found in level II and III with statistical significance (p value = 0.022). The male prevalence also revealed in both numerical and structural abnormalities in level II and level III, but no difference in the cases of level I. Conclusion: In conclusion, our observation showed a novel finding of higher male prevalence of CM in level II and III, and both in numerical and structural abnormalities. It's consistent with the theory of better survival in male embryo after partial self-correction of initial chromosomal aberrations, male-specific selection against chromosomal abnormalities.

Objective: We present prenatal diagnosis of low-level mosaicism for tetrasomy 18p at amniocentesis in a pregnancy with a favorable outcome. Case Report: A 40-year-old woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a de novo supernumerary isochromosome 18p in eight of 39 colonies of cultured amniocytes. The karyotype was 47,XX,+i(18)(p10)[8]/46,XX[31]. Array comparative genomic hybridization (aCGH) analysis using uncultured amniocytes revealed arr 18p11.32p11.21 [hg 19] (148,963–14,081,887) × 2–3. Repeat amniocentesis was performed at 20 weeks of gestation. Interphase fluorescence in situ hybridization (FISH) analysis showed four 18p11.22-specific probe (RP11-918F20) signals in 11.7% (12/103 cells) of uncultured amniocytes. aCGH analysis on uncultured amniocytes did not detect genomic imbalance in chromosome 18. The parental karyotypes were normal. Polymorphic DNA marker analysis excluded uniparental disomy 18. Cytogenetic analysis of cultured amniocytes at repeat amniocentesis revealed a karyotype of 47,XX,+i(18)(p10)[2]/46,XX[12]. Prenatal ultrasound was unremarkable. The pregnancy was carried to 38 weeks of gestation, and a 2742-g phenotypically normal female baby was delivered with a cord blood karyotype of 46,XX. When examined at 8 months of age, the infant was normal in growth and psychomotor development. Interphase FISH analysis on 21 uncultured urinary cells revealed normal signals in all cells and no mosaic tetrasomy 18p. Conclusion: Low-level mosaic tetrasomy 18p at amniocentesis without ultrasound abnormalities can be associated with a favorable outcome.

Objective: We present the association of paternal uniparental disomy (UPD) 9 with mosaicism for a small supernumerary marker chromosome 9 [sSMC(9)] and a supernumerary ring chromosome 9 [r(9)]. Materials and methods: A 38-year-old woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 47,XY,+mar [25]/48,XY,+mar,+r(9) [4]/47,XY,+r(9) [1]/46,XY [6]. The parental karyotypes were normal. Array comparative genomic hybridization (aCGH) of cultured amniocytes revealed a result of de novo 9p13.1q21.11 (38,792,472–71,026,063) × 2.64. The marker chromosome was determined to be an sSMC(9) by spectral karyotyping and aCGH. A phenotypically normal baby was delivered at 38 weeks of gestation. During pediatric follow-ups at age two years, the neonate manifested normal psychomotor and growth development. Cytogenetic analysis, metaphase fluorescence in situ hybridization (FISH), single nucleotide polymorphism (SNP) aCGH and polymorphic DNA marker analysis were performed on the peripheral blood of the neonate. Results: The neonate's blood had the following results. Metaphase FISH confirmed coexistence of the sSMC(9) and the supernumerary r(9). The karyotype was 47,XY,+sSMC(9) [14]/48,XY, +sSMC(9),+r(9) [10]/47,XY,+r(9) [6]/46,XY [10]. SNP aCGH revealed arr 9p22.3q21.11 (14,234,165–71,035,608) × 2–3, arr 9p24.3p22.3 (216,123–14,629,321)hmz, arr 9p21.3p13.2 (24,769,722–36,732,597)hmz and arr 9q21.11q34.3 (71,013,799–141,011,581)hmz. Polymorphic DNA marker analysis showed paternal isodisomy 9. Conclusion: Individuals with mosaicism for sSMC(9) and supernumerary r(9) may be associated with paternal UPD 9.

Objective: We present prenatal diagnosis and molecular cytogenetic characterization of a small supernumerary marker chromosome (sSMC) derived from chromosome 16. Case report: A 28-year-old woman underwent amniocentesis at 17 weeks of gestation because of abnormal maternal serum screening for Down syndrome. Amniocentesis revealed a karyotype of 47,XY,+mar[5]/46,XY[9]. Parental karyotypes were normal. Prenatal ultrasound findings were unremarkable. Array comparative genomic hybridization (aCGH) analysis of cultured amniocytes revealed a de novo 16% gene dosage increase of 16q11.2-q22.1. Repeat amniocentesis at 21 weeks of gestation revealed a karyotype of 47,XY,+mar[10]/46,XY[31]. aCGH analysis of uncultured amniocytes revealed a result of arr 16q11.2q22.1 (46,492,626–68,867,969) × 2.20 with a log2 ratio of 0.15 encompassing RPGRIP1L, FTO, SLC6A2, BBS2 and CDH1. Interphase fluorescence in situ hybridization (FISH) analysis on uncultured amniocytes detected partial trisomy 16q in 36/137 (26.3%) of uncultured amniocytes. Polymorphic DNA marker analysis on amniocytes and parental bloods excluded uniparental disomy 16. Premature labor occurred at 25 weeks of gestation, and a 585-g male baby without craniofacial dysmorphism was delivered and survived. At age 1½ years, pediatric follow-ups revealed normal psychomotor development, normal body weight, short stature, congenital hypothyroidism, hearing impairment and hypospadias in the neonate, and the peripheral blood had a karyotype of 46,XY in 40 cultured lymphocytes. Conclusion: aCGH, interphase FISH and polymorphic DNA marker analyses of uncultured amniocytes are useful for confirmation of prenatally detected mosaic sSMCs at amniocentesis.

Objective: We present prenatal diagnosis and molecular cytogenetic characterization of concomitant familial small supernumerary marker chromosome 4 [sSMC(4)] derived from 4q11.1–q12 and q13.2, and 5q13.2 microdeletion with no apparent phenotypic abnormality. Materials and methods: A 32-year-old woman underwent amniocentesis at 21 weeks of gestation because of absent nasal bone on fetal ultrasound. Amniocentesis revealed a karyotype of 47,XX,+mar[13]/46,XX[3]. Array comparative genomic hybridization analysis on the cultured amniocytes revealed a 2.752-Mb duplication at 4q11–q12, a 1.949-Mb duplication at 4q13.2, and a 1.65-Mb deletion at 5q13.2. The woman underwent repeat amniocentesis at 24 weeks of gestation for molecular cytogenetic characterization. The phenotypically normal parents and their elder son underwent genetic analysis. Results: At repeat amniocentesis, interphase fluorescence in situ hybridization analysis on uncultured amniocytes revealed 79.25% (84/106) mosaicism for the sSMC(4), and metaphase fluorescence in situ hybridization analysis on cultured amniocytes revealed that all 20 cells examined (100%) had the sSMC(4). Polymorphic DNA marker analysis on uncultured amniocytes excluded uniparental disomy 4. The father had a karyotype of 47,XY,+mar[2]/46,XY[38], and interphase fluorescence in situ hybridization revealed 2.91% (3/103) mosaicism for the sSMC(4) in his peripheral blood. The mother carried the 5q13.2 microdeletion. The elder son had a karyotype of 47,XY,+mar[27]/ 46,XY[13] with duplications of 4q11–q12 and 4q13.2. A 3105 g female baby was delivered at term with no apparent phenotypic abnormality. Conclusion: Prenatal diagnosis of concomitant sSMC and microdeletion should raise a suspicion of familial inheritance.

Objective: We present prenatal diagnosis of low-level mosaic trisomy 12. Case Report: A 40-year-old woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age, which revealed a karyotype of 47,XX,+12[5]/46,XX[24] consistent with 17.2% (5/29) mosaicism for trisomy 12. Repeat amniocentesis performed at 21 weeks of gestation revealed a karyotype of 47,XX,+12[4]/46,XX[6] consistent with 40% (4/10) mosaicism for trisomy 12. Interphase fluorescence in situ hybridization (FISH) on 112 uncultured amniocytes detected 23 cells with trisomy 12 consistent with 20.5% (23/112) mosaicism for trisomy 12. Polymorphic DNA marker analysis excluded uniparental disomy 12. Array comparative genomic hybridization (aCGH) on uncultured amniocytes revealed a result of arr 12p13.33q24.33 (230,451–133,773,499) × 2.2, 17p12 (14,191,925–15,442,037) × 1.0 consistent with 10–20% mosaic trisomy 12. The father carried the 17p12 microdeletion. The fetal ultrasound findings were unremarkable. A 3958-g female fetus was delivered at 37 weeks of gestation with no phenotypic abnormality. The cord blood had a karyotype of 46,XX. Postnatal interphase FISH on urinary cells revealed 7.14% (7/98) mosaicism for trisomy 12. Conclusion: Low-level mosaic trisomy 12 at amniocentesis can be associated with a favorable pregnancy outcome. Interphase FISH and aCGH on uncultured amniocytes are useful for confirmation of low-level mosaic trisomy 12 at amniocentesis.

Objective: We present prenatal diagnosis and molecular genetic analysis of mosaic trisomy 17 and a review of the literature of mosaic trisomy 17 at amniocentesis. Materials and Methods: A 42-year-old woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age, which revealed a karyotype of 47,XX,+17[4]/46,XX[17]. Prenatal ultrasound findings were unremarkable. She underwent repeat amniocentesis at 20 weeks of gestation. Interphase fluorescence in situ hybridization (FISH), array comparative genomic hybridization, and quantitative fluorescent polymerase chain reaction assays were applied to uncultured amniocytes. Conventional cytogenetic analysis was applied to cultured amniocytes and cord blood. Interphase FISH was applied to uncultured urinary cells postnatally. Results: At repeat amniocentesis, molecular genetic analysis of uncultured amniocytes revealed no genomic imbalance in array comparative genomic hybridization, no uniparental disomy 17 in quantitative fluorescent polymerase chain reaction, and 4.7% (5/105 cells) mosaic trisomy 17 in interphase FISH analysis. Conventional cytogenetic analysis of cultured amniocytes revealed a karyotype of 46,XX (17/17 colonies). A phenotypically normal baby was delivered at 38 weeks of gestation. The cord blood had a karyotype of 46,XX. Interphase FISH analysis of uncultured urinary cells revealed 5.6% (5/90 cells) mosaic trisomy 17. The neonate manifested normal growth and psychomotor development during follow-ups. Conclusion: Low-level mosaicism for trisomy 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 genetic counseling. A review of the literature shows a correlation between an adverse fetal outcome and a higher trisomy 17 mosaicism level at amniocentesis associated with ultrasound abnormality.

Objective: To present molecular cytogenetic characterization of inv dup del(8p) in a fetus with congenital malformations. Materials and Methods: A 19-year-old, primigravid woman underwent cord blood sampling at 31 weeks of gestation because of prenatal ultrasound findings of polyhydramnios, intestinal obstruction, right ventriculomegaly, and hypoplastic left heart. Preterm precipitous labor and delivery occurred at 32 weeks of gestation. Array comparative genomic hybridization (aCGH), conventional cytogenetic analysis and metaphase fluorescence in situ hybridization (FISH) were applied on cord blood lymphocytes. aCGH was also applied on the umbilical cord. Conventional cytogenetic analysis was applied on parental bloods. Results: aCGH detected an 11.35 Mb deletion in 8p23.3-p23.1 encompassing SOX7 and GATA4, and a 31.99 Mb duplication in 8p23.1-p11.1 in the fetus. Metaphase FISH confirmed inv dup del(8p). The fetus had a karyotype of 46,XX,der(8)del(8)(p23.1) inv dup(8) (p11.1p23.1). Parental karyotypes were normal. A malformed fetus was delivered with facial dysmorphism. Conclusion: Fetuses with inv dup del(8p) may present central nervous system (CNS) abnormality and congenital heart defect on prenatal ultrasound. Prenatal diagnosis of concomitant CNS and cardiac abnormalities should include a differential diagnosis of chromosome 8p inverted duplication deletion syndrome.

Objective: We present the application of non-invasive prenatal testing (NIPT) in late gestation in a pregnancy associated with intrauterine growth restriction (IUGR) and trisomy 22 confined placental mosaicism (CPM). Case report: A 35-year-old pregnant woman underwent chorionic villus sampling (CVS) at 12 weeks of gestation. The pregnancy was conceived by in vitro fertilization and intracytoplasmic sperm injection. CVS revealed a karyotype of 47,XY,+22 in all of 15 cultured chorionic villi cells. Array comparative genomic hybridization analysis on uncultured chorionic villi revealed a result consistent with trisomy 22. The woman underwent amniocentesis at 17 weeks of gestation. Amniocentesis revealed a karyotype of 46,XY in all 20 colonies of cultured amniocytes. Additional polymorphic DNA marker analysis excluded uniparental disomy 22. The parental karyotypes were normal. Prenatal ultrasound at 23 weeks of gestation revealed fetal retrognathia, IUGR and a calcified placenta. NIPT at 27 weeks of gestation using maternal plasma cell-free DNA analysis showed a chromosome Z-score of 5.74 for chromosome 22 (the Z-score for each pair of chromosomes is defined as “increased” if >3), indicating an abnormal placenta with trisomy 22 CPM leading to IUGR in the fetus. At 36 weeks of gestation, a 1754-g male fetus was delivered with cleft palate and imperforate anus but no other phenotypic abnormalities. The cord blood had a karyotype of 46,XY (40/40 cells), the umbilical cord had a karyotype of 47,XY,+22[9]/46,XY[31], and the placental tissues had a karyotype of 47,XY,+22[15]/46,XY[25]. Conclusion: NIPT in late gestation is useful in detection of placental abnormality associated with CPM and IUGR but a normal karyotype at amniocentesis.

Objective: The aim of this research was to present prenatal diagnosis of Langer-Giedion syndrome (LGS/TRPS type II) and Cornelia de Lange syndrome-4 (CDLS4). Materials and methods: A 36-year-old woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Conventional cytogenetic analysis of amniocentesis revealed an interstitial deletion of chromosome 8q or del(8)(q23.3q24.13). Level II prenatal ultrasound examination revealed craniofacial dysmorphism. The pregnancy was terminated, and a malformed fetus was delivered with characteristic craniofacial dysmorphism of LGS/TRPS type II and CDLS4. Whole-genome array comparative genomic hybridization (aCGH) on the DNA extracted from cultured amniocytes was performed. Results: The analysis by aCGH revealed a result of arr 8q23.3q24.11 (116,087,006–118,969,399)×1, 8q24.13 (123,086,851–124,470,847)×1 (NCBI build 37) with a 2.88-Mb deletion of 8q23.3–q24.11 encompassing six OMIM genes, TRPS1, EIF3H, RAD21, SLC30A8, MED30, and EXT1, and a 1.383-Mb deletion of 8q24.13 encompassing four OMIM genes, ZHX2, DERL1, ZHX1, and ATAD2. Conclusion: In the present case, the conventional cytogenetic analysis of cultured amniocytes revealed del(8)(q23.3q24.13), whereas aCGH analysis of cultured amniocytes showed the deletions of 8q23.3–q24.11 and 8q24.13 with the presence of the segment 8q24.12. Therefore, aCGH provides the advantage of better understanding of the nature of interstitial deletion and genotype–phenotype correlation in this case.

Objective: To present perinatal detection of distal 3p duplication and terminal 7q deletion associated with nuchal edema and cyclopia in a fetus, and to review the literature. Materials and methods: A 32-year-old, G9P0, woman who had experienced eight spontaneous abortions was found to have fetal nuchal edema, alobar holoprosencephaly, and cyclopia by prenatal ultrasound at 15 weeks of gestation. The pregnancy was subsequently terminated, and a malformed fetus was delivered with cyclopia. Molecular and conventional cytogenetic analyses were made to determine the genetic pathogenesis of fetal abnormalities. Results: The father had a karyotype of 46,XY,t(3;7)(p22.1;q36.1). The mother had a karyotype of 46,XX. The fetus had a karyotype of 46,XY,der(7)t(3;7)(p22.1;q36.1)pat. The analysis of array comparative genomic hybridization analysis revealed a 43.68-Mb duplication of 3p26.3-3p22.1 encompassing CHL1 and CNTN4, and an 8.66-Mb deletion of 7q36.1-7q36.3 encompassing SHH in the fetus. Conclusion: Simultaneous occurrence of 7q deletion and 3p duplication can be associated with alobar holoprosencephaly. For the couple with a parental translocation involving 7q and 3p, prenatal ultrasound should include a detailed investigation of central nervous system anomalies.

Objective: This study aims to present molecular cytogenetic characterization of Pallister–Killian syndrome (PKS). Materials and methods: A 37-year-old woman underwent amniocentesis at 18 weeks of gestation. Amniocentesis revealed a karyotype of 47,XY,+i(12)(p10)[6]/48,XY,+i(12)(p10)×2[1]/46,XY[6]. Repeated amniocentesis was performed at 20 weeks of gestation. Array comparative genomic hybridization (aCGH) was performed using uncultured amniocytes, cord blood, and skin. Quantitative fluorescent polymerase chain reaction (QF-PCR) was performed using uncultured amniocytes and parental bloods. Interphase fluorescence in situ hybridization (FISH) analysis was performed using uncultured amniocytes and cultured stimulated cord blood lymphocytes. Conventional cytogenetic analysis was performed using cultured cells from amniotic fluid, skin, placenta, umbilical cord, and cord blood. Results: Repeated amniocentesis revealed a mosaic tetrasomy 12p level of 25% (10/40), cultured cord blood lymphocytes had no mosaicism, cultured skin fibroblasts had a mosaic tetrasomy 12p level of 52.5% (21/40), umbilical cord fibroblasts had a mosaic tetrasomy 12p level of 72.5% (29/40), and the placental cells had a mosaic tetrasomy 12p level of 2.5% (1/40) on conventional cytogenetics. An aCGH analysis revealed that the increases in gene dosage in 12p for uncultured amniocytes, skin, and cord blood were the log2 ratios of 0.9, 0.7, and 0.7, respectively. Interphase FISH on uncultured amniocytes revealed a mosaic level of 73.1% (49/67) (tetrasomy 12p: 33; hexasomy 12p: 16). Interphase FISH analysis of stimulated cultured cord blood lymphocytes revealed a mosaic level of 58.3% (60/103) (tetrasomy 12p: 51; hexasomy 12p: 9). Conclusion: In the diagnosis of PKS by conventional culture cytogenetics, cord blood samplings and placental samplings are prone to a negative result when compared with amniocentesis. Whenever cord blood sampling is applied for prenatal diagnosis of PKS, aCGH on uncultured cord blood or interphase FISH on cultured cord blood can be used for the diagnosis, in addition to conventional cytogenetics.

Objective: The aim of this study is to present the incidence, prenatal and postnatal findings, and modes of ascertainment in chromosomal deletions detected at amniocentesis. Materials and methods: We reviewed all the cases with chromosomal deletions, which were detected by amniocentesis in Mackay Memorial Hospital, Taipei, Taiwan, between January 1987 and December 2012. Data on the locations and types of deletion, reasons for performing amniocentesis, maternal age, gestational age at amniocentesis, fetal karyotypes, inheritance of deletions, and relative prenatal findings were collected. Results: Amniocentesis was performed in 33,305 cases within this period of time. Among these, 31 cases of chromosomal deletions were considered for the study. The mean gestational age at amniocentesis was 21.0 weeks (range from 15 weeks to 32 weeks) and the mean maternal age at amniocentesis was 32.1 years (range from 26 years to 37 years). Nineteen cases (61.3%) manifested fetal structural abnormalities on ultrasound, nine (29.0%) presented no ultrasound abnormalities, and three had an unknown status. The main modes of ascertainment included abnormal ultrasound findings in 10 cases (32.2%), advanced maternal age in 11 cases (35.5%), abnormal maternal serum screening results in six cases (19.6%), and other reasons in four cases (13.0%). Of the 27 cases with known inheritance, the deletion was inherited in two (6.6%) and de novo in 25 (92.6%). Males accounted for 11 (35.5%) and females for 20 (64.5%) cases. Chromosomal deletions are more often to occur in chromosomal 5(4 cases, 12.9%), chromosomal 18 (4 cases, 12.9%), chromosomal 4 (3 cases, 9.7%), chromosomal 7 (3 cases, 9.7%), chromosomal 10 (3 cases, 9.7%), chromosomal 11 (3 cases, 9.7%), and chromosomal 1 (2 cases, 6.5%). There were four cases of chromosomal mosaicism: two involved chromosome 5, one involved chromosome 10, and one involved chromosome 18. Twenty-three cases (74.2%) had terminal deletions and the other eight cases (26.7%) had interstitial-type deletions. Conclusion: In summary, we have presented the results of prenatal diagnosis for chromosomal deletions using amniocentesis. Chromosomal deletions are more likely to occur in females and more often in chromosomal 5p and 18q. Prenatal diagnosis at amniocentesis is frequently associated with advanced maternal age, abnormal ultrasound findings, and abnormal maternal serum screening. The frequency of ascertainment in chromosome deletion seems to be directly correlated with advanced maternal age and abnormal ultrasound findings. In cases with terminal deletions, prenatal ultrasound plays a more important role for prenatal diagnosis.

Objective: This study aims at presenting prenatal diagnosis of mosaic trisomy 2 and reviewing the literature. Materials, Methods, and Results: A 32-year-old woman underwent amniocentesis at 21 weeks of gestation because of abnormal maternal serum biochemistry. Amniocentesis revealed a karyotype of 47,XY,+2[1]/46,XY[21] in in situ cultures. The single colony with trisomy 2 had two metaphase cells, and both had the karyotype of 47,XY,+2. Repeated amniocentesis was performed at 23 weeks of gestation. Interphase fluorescence in situ hybridization (FISH) analysis on uncultured amniocytes using a 2q11.1-specific probe RP11-468G5 (spectrum green) showed three green signals in 11 of 47 uncultured amniocytes, indicating 23.4% mosaicism for trisomy 2. The cultured amniocytes had a karyotype of 46,XY[20 colonies]. Polymorphic DNA marker analysis excluded uniparental disomy 2. The woman underwent the third amniocentesis at 25 weeks of gestation. Interphase FISH analysis on uncultured amniocytes revealed 9.4% (5/53 cells) mosaicism for trisomy 2. The cultured amniocytes had a karyotype of 46,XY[30 colonies]. Prenatal ultrasound was normal. The parents decided to continue the pregnancy to term, and a 3316-g baby was delivered with no phenotypic abnormalities. Cord blood had a karyotype of 46,XY[40 cells]. Interphase FISH analysis on uncultured urinary cells revealed 8.2% (4/49 cells) mosaicism for trisomy 2. The neonate was normal in growth and psychomotor development at 6 months of age. Conclusion: Prenatal diagnosis of a single colony with two or more cells with trisomy 2 at amniocentesis should alert a clinically significant aneuploidy, and interphase FISH on uncultured amniocytes is useful for rapid confirmation of low-level trisomy 2 mosaicism at amniocentesis. The abnormal cell line of trisomy 2 may disappear after long-term amniocyte cultures.

Objective: This study aimed at presenting prenatal diagnosis and molecular cytogenetic characterization of a small supernumerary marker chromosome (sSMC) derived from chromosome 8 by fluorescence in situ hybridization (FISH), quantitative fluorescent polymerase chain reaction (QF-PCR), and array comparative genomic hybridization (aCGH) on uncultured amniocytes. Materials, Methods, and Results: A 32-year-old woman underwent amniocentesis at 19 weeks of gestation because of fetal pyelectasis. Amniocentesis revealed a de novo ring-shaped sSMC in two of 21 colonies of cultured amniocytes. Repeated amniocentesis at 22 weeks of gestation revealed a karyotype of 47,XY,+mar[8]/46,XY[32] in cultured amniocytes. Spectral karyotyping and FISH confirmed that the sSMC was derived from chromosome 8. She underwent a third amniocentesis at 26 weeks of gestation. Oligonucleotide-based aCGH analysis on uncultured amniocytes demonstrated a 43 Mb genomic gain in chromosome 8 encompassing 8p22→q12.1. Polymorphic DNA marker analysis of the uncultured amniocytes revealed a maternal origin of the sSMC and excluded uniparental disomy 8. Interphase FISH analysis showed three D8Z2 signals in 8/40 (20%) of uncultured amniocytes. The cultured amniocytes had a karyotype of 47,XY,+r(8)(p22q12.1)[3]/46,XY[37]. The pregnancy was carried to term, and an apparently normal baby, weighing 3300 g, was delivered with mild hydronephrosis but no other phenotypic abnormalities. The cord blood was found to have a karyotype of 47,XY,+r(8)(p22q12.1)[2]/46,XY[38]. Conclusion: Prenatal diagnosis of fetal pyelectasis should alert obstetricians of chromosome aberration. Interphase FISH, QF-PCR, and aCGH analyses on uncultured amniocytes are helpful in rapid positive confirmation of an sSMC detected at amniocentesis.

Objective: To present the prenatal diagnosis and molecular investigation of the parental origin and mechanism of nondisjunction underlying an 48,XXY,+18 karyotype in a fetus with congenital abnormalities, and to review the literature. Materials, Methods, and Results: A 42-year-old woman was referred for amniocentesis at 18 weeks of gestation because of advanced maternal age. Prenatal ultrasound revealed bilateral choroid plexus cysts. Amniocentesis revealed a karyotype of 48,XXY,+18. The parental karyotypes were normal. Level II ultrasound revealed a flexion contracture deformity of the left wrist with absence of the thumb. The pregnancy was terminated at 22 weeks of gestation. A 332 g male fetus was delivered with clenched hands, arthrogryposis of the left wrist, aplasia of the left thumb, micrognathia, low-set ears, hypertelorism, rocker-bottom feet, and a normal penis. Quantitative fluorescent polymerase chain reaction assays using polymorphic DNA markers showed a triallelic pattern with a dosage ratio of 1:1:1 (paternal:maternal:maternal) for chromosome 18-specific markers, and a monoallelic pattern of a single maternal allele for chromosome X-specific markers. The fetus inherited two copies of two different maternal alleles on chromosome 18, and two copies of a single maternal allele on chromosome X. The molecular result, along with the karyotype of 48,XXY,+18, was consistent with the occurrence of nondisjunction of chromosome 18 in a maternal meiosis I error and nondisjunction of chromosome X in a maternal meiosis II error or less likely a postzygotic mitotic error. Conclusion: The present case provides evidence that abnormal separation of chromosomes 18 and X resulting in double aneuploidy may occur in different cell divisions, and such an occurrence is related to advanced maternal age.

Objective: To present array comparative genomic hybridization (aCGH) characterization of partial monosomy 13q (13q21.32→qter) and partial trisomy 8p (8p12→pter) presenting with anencephaly and increased nuchal translucency (NT). Case Report: A 34-year-old primigravid woman was referred to the hospital at 12 weeks of gestation for termination of the pregnancy because of major structural abnormalities of the fetus. Prenatal ultrasound revealed a malformed fetus with anencephaly and an increased NT thickness of 5 mm at 12 weeks of gestation. Cytogenetic analysis of the fetus revealed a derivative chromosome 13. The mother was subsequently found to carry a balanced reciprocal translocation between 8p12 and 13q21. Bacterial artificial chromosome-based aCGH using fetal DNA demonstrated partial trisomy 8p and partial monosomy 13q [arr cgh 8p23.3p12 (RP11-1150M5→RP11-1145H12)×3, 13q21.32q34 (RP11-326B4→RP11-450H16)×1]. Oligonucleotide-based aCGH showed a 36.7-Mb duplication of distal 8p and a 48.4-Mb deletion of distal 13q. The fetal karyotype was 46,XY,der(13) t(8;13)(p12;q21.32)mat. The maternal karyotype was 46,XX,t(8;13)(p12;q21.32). Conclusion: The 13q deletion syndrome can be associated with neural tube defects and increased NT in the first trimester. Prenatal sonographic detection of neural tube defects should alert chromosomal abnormalities and prompt cytogenetic investigation, which may lead to the identification of an unexpected parental translocation involving chromosomal segments associated with neural tube development.

Objective: To present prenatal diagnosis and molecular cytogenetic characterization of mosaicism for a small supernumerary marker chromosome (sSMC) derived from ring chromosome, or r(4) by spectral karyotyping (SKY), fluorescence in situ hybridization (FISH), and array comparative genomic hybridization (aCGH). Materials, Methods, and Results: A 37-year-old, primigravid woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age. Amniocentesis revealed a de novo ring-shaped sSMC in 16 of 31 amniocyte colonies. The parental karyotypes were normal. Level II ultrasound findings were unremarkable. Repeated amniocentesis revealed a karyotype of 47,XX,+mar[17]/46,XX[19]. The sSMC was characterized by SKY and FISH, which showed a chromosome 4 origin of the sSMC. aCGH demonstrated a 21.7-Mb gain in the gene dosage encompassing the region of 4p12→q13.2. The sSMC was r(4)(p12q13.2). The fetal karyotype was 47,XX,+r(4)(p12q13.2)[17]/46,XX[19]. The pregnancy was subsequently terminated. The fetus postnatally manifested hypertelorism, epicanthic folds, a prominent nose, a triangular face, low-set ears, clinodactyly of the fingers, and small big toes. Postnatal cytogenetic analyses of fetal and extraembryonic tissues revealed the karyotypes of 47,XX,+r(4)[18]/46,XX[21] in cord blood, 47,XX,+r(4)[20]/48,XX,+r(4),+r(4)[1]/46,XX[9] in umbilical cord, 47,XX,+r(4)[14]/47,XX,+dic r(4)[1]/46,XX[25] in skin, 47,XX,+r(4)[15]/46,XX[25] in amnion, and 47,XX,+r(4)[12]/47,XX,+dic r(4)[1]/46,XX[2] in placenta. Conclusion: SKY, FISH, and aCGH are helpful in genetic counseling of prenatally detected sSMCs by providing the immediate and thorough information on the origin and genetic component of the sSMC.

Objective: To present perinatal findings, modes of ascertainments, and modes of segregation in unbalanced reciprocal translocations detected at amniocentesis. Materials and Methods: Between January 1987 and July 2010, 40 cases with unbalanced reciprocal translocations were diagnosed by amniocentesis at Mackay Memorial Hospital, Taipei, Taiwan. The 40 cases originated from 29 families; 21 families with one case, 7 families with two cases, and 1 family with five cases. Results: Of 40 cases, 33 (82.5%) presented fetal ultrasound abnormalities and 7 (17.5%) presented no ultrasound abnormalities. Of 40 cases, 36 (90%) had a segregation mode of adjacent-1 2:2 segregation, 3 (7.5%) had a segregation mode of 3:1 segregation with tertiary trisomy, and 1 (2.5%) had a segregation mode of 3:1 segregation with tertiary monosomy. Of 29 families, 7 (24.1%) had de novo translocations and 22 (75.9%) had inherited translocations. In seven de novo cases, the main modes of ascertainments included abnormal ultrasound findings (n = 5) and advanced maternal age (n = 2). In 22 inherited families, the main modes of first ascertainment included abnormal ultrasound findings (n = 8), a previous aneuploid child (n = 8), advanced maternal age (n = 4), parental carrier status (n = 1), and abnormal maternal serum screening results (n = 1). Among 22 inherited families, 9 (40.9%) had a known parental carrier status, but 13 (59.1%) were unaware of parental carrier status at amniocentesis. Conclusion: Unbalanced reciprocal translocations detected at amniocentesis are frequently associated with abnormal ultrasound findings. Prenatal diagnosis of an unbalanced translocation may incidentally detect a balanced translocation in the family. Prenatal diagnosis of fetal structural abnormalities should alert structural chromosome rearrangements and prompt cytogenetic analysis of the fetus and parents if necessary.