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

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

Prenatal diagnosis of persistent left superior vena cava, polyhydramnios and a small gastric bubble in a fetus with VACTERL association.

OBJECTIVE: We reported a fetus that presenting with persistent left superior vena cava (PLSVC), polyhydramnios, and a small gastric bubble during prenatal examination and identified VACTERL association after birth. CASE REPORT: A 34-year-old woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age and the result was normal. Subsequently, an ultrasound revealed single umbilical artery (SUA) at 21 weeks of gestation. She received a detailed fetal anatomy survey that presented the same findings and PLSVC. A small visible gastric bubble was noted at that time, and the other organs were unremarkable. Polyhydramnios was identified at 30 weeks of gestation and amnioreduction was subsequently performed at 32 weeks of gestation. However, polyhydramnios was persisted despite amnioreduction and intrauterine growth restriction was also detected. A cesarean section was performed because of fetal distress at 36 + 2 weeks, and a 1832-g female baby was delivered. Pre-axial polydactyly at left thumb, SUA and esophageal atresia with distal tracheoesophageal fistula (TEF) were identified after birth. The neonate died at age of 4 days because of surgical complication following esophageal anastomosis. CONCLUSION: Prenatal diagnosis of PLSVC associated with polyhydramnios and a small gastric bubble may indicate esophageal atresia with TEF, and further examination for associated syndromes such as VACTERL association is warranted.

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

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

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

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

Prenatal diagnosis of a familial Y long-arm and chromosome 15 short-arm translocation inherited from a mother carrier.

OBJECTIVE: We present prenatal diagnosis of a familial Y long-arm and chromosome 15 short-arm translocation inherited from a mother carrier. CASE REPORT: A 34-year-old primigravid woman underwent amniocentesis at 20 weeks of gestation because of advanced maternal age. Amniocentesis revealed a derived chromosome 15 or 15p+ with an additional material on the short arm of chromosome 15. Cytogenetic analysis of the parents revealed that the phenotypically normal mother carried the same 15p+ variant, and the father had a karyotype of 46,XY. Array comparative genomic hybridization (aCGH) analysis on the DNA extracted from cultured amniocytes revealed no genomic imbalance. Polymorphic DNA marker analysis using the DNAs extracted from cultured amniocytes and parental bloods excluded uniparental disomy (UPD) 15. C-banded preparations and metaphase fluorescence in situ hybridization analysis using a Yq12-specific probe showed a positive stain on the 15p+, indicating the origin of Yq on the short arm of the derivative chromosome 15. The karyotype of amniocentesis was 46,XX,der(15)t(Y;15)(q12;p13)mat. The mother had a karyotype of 46,XX,der(15) t(Y;15)(q12;p13). At 39 weeks of gestation, a 3006-g healthy female baby was delivered with no phenotypic abnormality. During follow-up at age six months, she manifested normal physical and psychomotor development. CONCLUSION: Prenatal diagnosis of a 15p+ variant should include a differential diagnosis of genomic imbalance and UPD 15, and aCGH and polymorphic DNA marker analyses are useful under such a circumstance.

Prenatal diagnosis and molecular cytogenetic characterization of a small supernumerary marker chromosome derived from chromosome 15 in a pregnancy associated with recurrent Down syndrome.

OBJECTIVE: We present prenatal diagnosis and molecular cytogenetic characterization of a small supernumerary marker chromosome (sSMC) derived from chromosome 15 in a pregnancy associated with recurrent Down syndrome. CASE REPORT: A 33-year-old, gravida 4, para 2, woman underwent amniocentesis at 16 weeks of gestation because of a previous child with Down syndrome and a karyotype of 46,XY,der(14;21)(q10; q10),+21. In this pregnancy, amniocentesis revealed a karyotype of 47,XX,+21[12]/48,XX,+21,+mar[3]. The parental karyotypes were normal. The pregnancy was terminated, and a malformed fetus was delivered with characteristic craniofacial appearance of Down syndrome and hypoplastic middle phalanx of the fifth fingers. The placenta had a karyotype of 47,XX,+21[37]/48,XX,+21,+mar[3]. The umbilical cord had a karyotype of 47,XX,+21[38]/48,XX,+21,+mar[2]. In addition to trisomy 21, array comparative genomic hybridization (aCGH) on the DNA extracted from umbilical cord revealed 40∼50% mosaicism for a 2.604-Mb duplication of 15q25.2-q25.3, or arr 15q25.2q25.3 (83,229,665-85,834,131) × 2.4 [GRCh37 (hg19)] encompassing 19 Online Mendelian Inheritance in Man (OMIM) genes. Quantitative fluorescent polymerase chain reaction (QF-PCR) using the DNAs extracted from cultured amniocytes and parental bloods revealed maternal origin of the sSMC(15) and the extra chromosome 21. CONCLUSION: aCGH is useful for identification of the nature of sSMC, and QF-PCR is useful for determination of the parental origin of the aberrant chromosomes.

Prenatal diagnosis and molecular cytogenetic characterization of a pure ring chromosome 21 with a 4.657-Mb 21q22.3 deletion.

OBJECTIVE: We present diagnosis and molecular cytogenetic characterization of a pure ring chromosome [r(21)] with a 4.657-Mb 21q22.3 deletion. CASE REPORT: A 44-year-old woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype 46,XX,r(21)(p11.2q22.3). Prenatal ultrasound findings were unremarkable. Simultaneous array comparative genomic hybridization (aCGH) analysis on uncultured amniocytes revealed a 4.657-Mb deletion at 21q22.3. The parental karyotypes were normal. The pregnancy was subsequently terminated, and a malformed fetus was delivered with facial dysmorphism and clinodactyly. Postnatal cytogenetic analysis of umbilical cord revealed a karyotype of 46,XX,r(21)(p11.2q22.3). aCGH analysis of umbilical cord revealed the result of arr 21q22.3 (43,427,188-48,084,156) × 1.0 with a 4.657-Mb 21q22.3 deletion encompassing 57 Online Mendelian Inheritance in Man (OMIM) genes including TRPM2, TSPEAR, COL18A1, COL6A1, COL6A2, LSS, PCNT, DIP2A, S100B and PRMT2. Metaphase fluorescence in situ hybridization (FISH) analysis of the umbilical cord fibroblasts confirmed a 21q22.3 deletion. CONCLUSION: Prenatal diagnosis of an r(21) should include molecular cytogenetic characterization such as aCGH and FISH to determine the extent of the 21q22.3 deletion.

Tetrasomy of 11q13.4-q14.3 due to an intrachromosomal triplication associated with paternal uniparental isodisomy for 11q14.3-qter, intrauterine growth restriction, developmental delay, corpus callosum dysgenesis, microcephaly, congenital heart defects and facial dysmorphism.

OBJECTIVE: We present tetrasomy of 11q13.4-q14.3 due to an intrachromosomal triplication associated with paternal isodisomy of uniparental disomy (iso-UPD) for 11q14.3-qter and multiple abnormalities. CASE REPORT: A 30-year-old primigravid woman was found to have intrauterine growth restriction (IUGR) in the fetus since 28 weeks of gestation, and a 2056-g baby was delivered at 38 weeks of gestation with fetal distress. The baby postnatally manifested hypotonia, microcephaly, facial dysmorphism of micrognathia, retrognathia and low-set ears, ventricular septal defect, atrial septal defect, tricuspid regurgitation and corpus callosum dysgenesis. A single nucleotide polymorphism (SNP) array comparative genomic hybridization analysis on the DNA extracted from the peripheral blood revealed the result of arr 11q13.4q14.3 (71,567,724-89,547,851) × 4, arr 11q14.3q25 (89,466,484-134,942,626) hmz [GRCh37 (hg19)] with a 17.980-Mb triplication of 11q13.4-q14.3 encompassing the genes of GRM5 and MAP6, and loss of heterozygosity for a 45.476-Mb region of 11q14.3-qter consistent with iso-UPD for 11q14.3-qter. Polymorphic DNA marker analysis confirmed paternal iso-UPD for 11q14.3-qter. Cytogenetic analysis of the blood revealed a karyotype of 46,XY,trp(11) (q13.4q14.3). The parental karyotypes were normal. When follow-ups at age 2 years, the neonate manifested physical and psychomotor developmental delay and intellectual disability. CONCLUSION: Tetrasomy 11q13.4-q14.3 may present the phenotype of IUGR, developmental delay, corpus callosum dysgenesis, microcephaly, congenital heart defects and facial dysmorphism.

Prenatal diagnosis of low-level mosaicism for a small supernumerary marker chromosome derived from chromosome 9q (9q13-q21.33) in a pregnancy with a favorable outcome, and cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes.

OBJECTIVE: We present prenatal diagnosis of low-level mosaicism for a small supernumerary marker chromosome (sSMC) derived from chromosome 9q (9q13-q21.33) in a pregnancy with a favorable outcome, and cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes. CASE REPORT: A 36-year-old, primigravid woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Cytogenetic analysis on cultured amniocytes revealed a karyotype of 46,XY in 20/20 colonies. Simultaneous array comparative genomic hybridization (aCGH) on the DNA extracted from uncultured amniocytes revealed 30% mosaicism for a de novo 20.3-Mb gene dosage increase at 9q13-q21.33. Repeat amniocentesis and cordocentesis were performed at 21 weeks of gestation. Cytogenetic analysis on cord blood revealed a karyotype of 47,XY,+mar [3]/46,XY [37]. aCGH analysis of cord blood revealed 7.5% mosaicism for a 17.15-Mb gene dosage increase at 9q21.11-q21.33. aCGH analysis of uncultured amniocytes revealed 11.7% mosaicism for a 17.15-Mb gene dosage increase at 9q21.11-q21.33. Polymorphic DNA marker analysis excluded uniparental disomy 9. The parental karyotypes were normal. The pregnancy was carried to 37 weeks of gestation, and a 2955-g phenotypically normal male baby was delivered. At birth, the cord blood had a karyotype of 47,XY,+mar [3]/46,XY [37], the placenta had a karyotype of 47,XY,+mar [10]/46,XY [30], and the umbilical cord had a karyotype of 47,XY,+mar [14]/46,XY [36]. aCGH analysis on the DNA extracted from cord blood at birth revealed no genomic imbalance. Interphase fluorescence in situ hybridization analysis on buccal mucosal cells at age two months detected 3.8% (4/106 cells) mosaicism for the sSMC, compared with 2% (2/100 cells) in the normal control. The neonate had normal physical development at age two months. CONCLUSION: Cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes may exist in the pregnancy with fetal mosaic sSMC. Low-level mosaicism for an sSMC derived from chromosome 9q13-q21.33 at prenatal diagnosis can be associated with a favorable outcome in the fetus.

Prenatal diagnosis of a 15q11.2-q14 deletion of paternal origin associated with increased nuchal translucency, mosaicism for de novo multiple unbalanced translocations involving 15q11-q14, 5qter, 15qter, 17pter and 3qter and Prader-Willi syndrome.

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.

Detection of paternal origin of fetal trisomy 18 in a pregnancy conceived by assisted reproductive technology and in vitro fertilization.

OBJECTIVE: We present detection of paternal origin of fetal trisomy 18 in a pregnancy conceived by assisted reproductive technology (ART) and in vitro fertilization (IVF). CASE REPORT: A 39-year-old woman underwent ART and IVF because of primary infertility. The woman was infertile because of myoma and endometriosis. Her husband was 39 years old, and the sperm analysis was normal. The couple was phenotypically normal. This pregnancy was conceived successfully by IVF. She received non-invasive prenatal testing at 11 weeks of gestation, the result showed a high risk for trisomy 18. She underwent chorionic villus sampling at 12 weeks of gestation, and the result was 47,XY,+18 in 24/24 cultured chorionic villi cells. Prenatal ultrasound findings were unremarkable. She underwent amniocentesis at 17 weeks of gestation, and the result was 47,XY,+18 in 20/20 colonies of cultured amniocytes. The pregnancy was subsequently terminated. Postnatal cytogeneic analysis confirmed the prenatal diagnosis. Polymorphic DNA marker analysis on the DNAs extracted from the umbilical cord and parental bloods showed a paternal origin of the extra chromosome 18, indicating a paternal origin of fetal trisomy 18. Cytogenetic analysis of paternal blood revealed a karyotype of 46,XY. CONCLUSION: Fetal trisomy 18 in pregnancies conceived by ART may be of paternal origin, and determination of paternal origin by polymorphic DNA marker analysis is useful for genetic counseling under such a circumstance.

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

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.

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

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

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.

OBJECTIVE: We 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 METHODS: We 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. RESULTS: Amniocentesis 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. CONCLUSIONS: Monozygotic twins discordant for low-level mosaic trisomy 17 at amniocentesis without ultrasound abnormalities can have a favorable outcome. Prenatal diagnosis of twins discordant for structural abnormalities and/or chromosomal aberrations should alert the possibility of monozygotic twinning, and QF-PCR testing is useful for rapid determination of zygosity and exclusion of UPD under such a circumstance.

Prenatal diagnosis of partial monosomy 2q (2q37.3→qter) and partial trisomy 10q (10q24.31→qter) of paternal origin associated with increased nuchal translucency and abnormal maternal serum screening results.

OBJECTIVE: We present prenatal diagnosis of terminal 2q deletion and distal 10q duplication of paternal origin in a fetus associated with increased nuchal translucency and abnormal maternal serum screening results. CASE REPORT: A 26-year-old woman who had experienced spontaneous abortion twice underwent amniocentesis at 16 weeks of gestation because of an increased nuchal translucency thickness of 3.5 mm at 12 weeks of gestation and abnormal maternal serum screening results of 2.573 multiples of the median (MoM) of free ß-human chorionic gonadotrophin (ß-hCG) and 1.536 MoM of pregnancy-associated plasma protein-A (PAPP-A) resulting in a trisomy 21 risk of 1:64. Amniocentesis revealed a derivative chromosome 2. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed arr [hg19] 2q37.3 (238,294,223-242,782,258) × 1, 10q24.31q26.3 (102,018,246-135,426,386) × 3. Cytogenetic analysis of parental bloods revealed a karyotype of 46,XX in the mother and a karyotype of 46,XY,t(2;10)(q37.3;q24.3) in the father. The fetal karyotype was 46,XX,der(2)t(2;10)(q37.3;q24.3)pat. The pregnancy was terminated at 20 weeks of gestation, and a malformed fetus was delivered with facial dysmorphism. Postnatal analysis of the cord blood confirmed the results of prenatal diagnosis. The fetus had a 4.693-Mb deletion of 2q37.3 encompassing the genes of HDAC4, KIF1A, PASK, HDLBP, FARP2 and D2HGDH, and a 33.34-Mb duplication of 10q24.31-q26.3 encompassing the gene of NFκB2. CONCLUSION: First-trimester ultrasound and maternal serum biochemistry screening may help to identify an unexpected unbalanced familial translocation at prenatal diagnosis.

Prenatal diagnosis and molecular cytogenetic characterization of a small supernumerary marker chromosome derived from inv dup(15).

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.

Prenatal diagnosis of mosaicism for trisomy 7 in a single colony at amniocentesis in a pregnancy with a favorable outcome.

OBJECTIVE: We present prenatal diagnosis of mosaicism for trisomy 7 in a single colony at amniocentesis 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 result of 47,XY,+7[1]/46,XY[26]. In 27 colonies of cultured amniocytes, all five cells in one colony had trisomy 7, while the rest 26 colonies had a normal karyotype. The parental karyotypes were normal. Repeat amniocentesis was performed at 19 weeks of gestation. Interphase fluorescence in situ hybridization (FISH) was applied on the uncultured amniocytes, and the result showed trisomy 7 signals in 4% (3/75 cells) of the uncultured amniocytes compared with 1.4% (1/70 cells) in the normal control. Uniparental disomy (UPD) 7 was excluded by polymorphic DNA marker analysis. The cultured amniocytes at repeat amniocentesis had a karyotype of 46,XY. Prenatal ultrasound findings were unremarkable. A healthy 3332-g male baby was delivered at 38 weeks of gestation. The karyotype of cord blood lymphocytes was 46,XY. The boy was phenotypically normal at age 8 months at follow-up. No trisomy 7 signal could be detected in the postnatal FISH analysis of the urinary cells. CONCLUSION: Mosaicism for trisomy 7 in a single colony at amniocentesis without UPD 7 can be associated with a favorable outcome.

Mosaic isochromosome 20q at amniocentesis: Prenatal diagnosis, genetic counseling and literature review.

OBJECTIVE: We present prenatal diagnosis of mosaic isochromosome 20q [i(20q)] at amniocentesis, and we review the literature. CASE REPORT: A 36-year-old woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 46,XY,i(20)(q10)[27]/46,XY[29]. Prenatal ultrasound findings were unremarkable. The parental karyotypes were normal. Repeat amniocentesis was performed at 20 weeks of gestation. During repeat amniocentesis, array comparative genomic hybridization (aCGH), interphase fluorescence in situ hybridization (FISH) and quantitative fluorescent polymerase chain reaction (QF-PCR) assay were performed on uncultured amniocytes, and conventional cytogenetic analysis, interphase FISH and aCGH were performed on cultured amniocytes. In the repeat amniocentesis, the cultured amniocytes revealed a karyotype of 46,XY. Interphase FISH analysis showed the i(20q) signal in 5.2% (5/96) of the uncultured amniocytes compared with 2% in the control, and in 0.98% (1/102) of the cultured amniocytes compared with 2% in the control. aCGH detected no genomic imbalance in both uncultured and cultured amniocytes. QF-PCR analysis excluded uniparental disomy 20. At 38 weeks of gestation, a healthy 2870-g male baby was delivered with no phenotypic abnormality. The postnatal blood karyotype was 46,XY. FISH analysis on urinary cells showed 2.1% (2/95 cells) mosaicism compared with 1.9% (2/105 cells) in the control. CONCLUSION: Mosaic i(20q) at amniocentesis is a benign condition associated with a favorable outcome in most cases and can be a cell culture artifact confined to cultured amniocytes. Molecular cytogenetic analysis using uncultured amniocytes is useful for rapid confirmation. Prenatal diagnosis of very high percentage of mosaicism for i(20q) at amniocentesis should alert the presence of fetal structural abnormalities. Prenatal diagnosis of mosaic i(20q) at amniocentesis should include a detail examination of fetal brain and spine.

Mosaic trisomy 22 at amniocentesis: Prenatal diagnosis and literature review.

OBJECTIVE: We present prenatal diagnosis of mosaic trisomy 22 at amniocentesis in a pregnancy with facial cleft, oligohydramnios and intrauterine growth restriction (IUGR), and we review the literature. CASE REPORT: A 37-year-old woman underwent amniocentesis at 19 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 47,XX,+22[9]/46,XX[9]. Array comparative genomic hybridization (aCGH) analysis on uncultured amniocytes showed a result of arr(22) × 3 [0.8]. Prenatal ultrasound revealed fetal median facial cleft, oligohydramnios and IUGR. Repeat amniocentesis at 22 weeks of gestation using uncultured amniocytes revealed an aCGH result of arr 22q11.1q13.33 (17,397,498-51,178,264) × 2.8 compatible with 80% mosaicism for trisomy 22, and a fluorescence in situ hybridization (FISH) result of mosaic trisomy 22 with trisomy 22 in 54/100 interphase cells. The cultured amniocytes at repeat amniocentesis had a karyotype of 47,XX,+22[12]/46,XX[8]. The parental karyotypes were normal. Polymorphic DNA marker analysis confirmed a maternal origin of the extra chromosome 22. The pregnancy was terminated, and a 256-g female fetus was delivered with facial dysmorphism and median facial cleft. Cytogenetic analysis of the skin fibroblasts revealed a karyotype of 47,XX,+22[33]/46,XX[7]. CONCLUSION: Fetuses with high level mosaicism for trisomy 22 at amniocentesis may present IUGR, facial cleft and oligohydramnios on prenatal ultrasound.

Digynic triploidy in a fetus presenting with semilobar holoprosencephaly.

OBJECTIVE: We present digynic triploidy in a fetus with semilobar holoprosencephaly (HPE). CASE REPORT: A 32-year-old, gravid 1, para 0, woman underwent prenatal ultrasound examination at 12 weeks of gestation, and the ultrasound showed relative macrocephaly, a small non-cystic placenta, and a fetus with absent nasal bone and semilobar HPE. The pregnancy was terminated subsequently, and a 50-g fetus was delivered with a relatively enlarged head and premaxillary agenesis. The placenta was small and non-cystic. Postnatal cytogenetic analysis of the umbilical cord revealed a karyotype of 69, XXX. Postnatal DNA marker analysis using quantitative fluorescent polymerase chain reaction assays and the polymorphic short tandem repeat markers for chromosome 18 and 20 on the placental tissues showed a diallelic pattern with a dosage of 1:2 (paternal allele to maternal allele ratio), indicating a maternal origin of the triploidy. CONCLUSION: Fetuses with digynic triploidy may present relative macrocephaly, semilobar HPE and a small placenta on prenatal ultrasound.