Prenatal diagnosis of mosaic distal 5p deletion and review of the literature

OBJECTIVES: To present the prenatal diagnosis of mosaic distal 5p deletion and a review of the literature. CLINICAL SUBJECT AND METHODS: A 37-year-old woman, gravida 2, para 1, underwent genetic amniocentesis at 17 weeks' gestation because of advanced maternal age. Cytogenetic analysis of the cultured amniocytes revealed mosaicism for a distal 5p deletion, mos 46,XX,del(5)(p15.1)/46,XX (23 colonies/23 colonies). Repeat amniocentesis showed a consistent karyotype of mos 46,XX,del(5)(p15.1)/46,XX (12 colonies/15 colonies). The parental karyotypes were normal. Prenatal ultrasound demonstrated microcephaly and cerebellar hypoplasia. The pregnancy was terminated at 21 weeks' gestation. Postnatally, the fetus displayed microcephaly, a triangular face, hypertelorism, epicanthic folds, down-slanting palpebral fissures, low-set ears, and micrognathia. A karyotype of mos 46,XX,del(5)(p15.1)/46,XX was found in the cord blood, liver, lungs, and skin, whereas the placenta had a different karyotype of mos 46,XX,dup(5)(qter-->p15.3::p15.3-->p10)/46,XX, and the karyotype of the amnion was mos 46,XX,del(5)(p15.1)/46,XX,dup(5)(qter-->p15.3::p15.3-->p10)/46,XX,trp(5)(qter-->p15.3::p15.3-->p10::p10-->p15.3)/46,XX. The deletion, duplication, and triplication of the terminal region of the short arm of chromosome 5 were confirmed by the studies of fluorescence in situ hybridization. CONCLUSION: The cri-du-chat syndrome can be identified prenatally because of advanced maternal age, familial cri-du-chat syndrome, parental balanced translocations involving chromosome 5, sonographically detected fetal structural abnormalities, and/or an abnormal maternal serum test. Fetuses with the mosaic distal 5p deletion may be associated with the sonographic findings of microcephaly and cerebellar hypoplasia, and fetoplacental and fetoamnionic chromosomal discrepancies.     

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

ObjectiveWe present prenatal diagnosis of mosaicism for trisomy 11 in a single colony at amniocentesis with a favorable outcome.Case ReportA 34-year-old woman underwent amniocentesis at 16 weeks of gestation because of advanced maternal age. Amniocentesis revealed a result of 47,XY,+11[1]/46,XY[9]. In 10 colonies of cultured amniocytes, all five cells in one colony had a karyotype of trisomy 11, while the rest nine 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 no trisomy 11 signals in 56/56 uncultured amniocytes. Uniparental disomy (UPD) 11 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 3084-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 10 months at follow-ups. The interphase FISH analysis on urinary cells revealed no trisomy 11 signal.ConclusionMosaicism for trisomy 11 in a single colony at amniocentesis without UPD 11 can be associated with a favorable outcome.     

Prenatal diagnosis of mosaic tetrasomy 18p

ObjectiveTo present prenatal diagnosis and molecular cytogenetic characterization of a small supernumerary marker chromosome derived from isochromosome 18p, by interphase fluorescence in situ hybridization (FISH) on uncultured amniocytes.Case ReportA 41-year-old woman underwent amniocentesis at 18 weeks of gestation, because of advanced maternal age. Amniocentesis revealed a de novo supernumerary isochromosome 18p in two of 14 colonies of cultured amniocytes. Repeated amniocentesis was performed at 22 weeks of gestation. Interphase FISH analysis on uncultured amniocytes showed four 18p11.32-specific probe (RP11-324G2) signals in 5.7% (3/53 cells) of uncultured amniocytes. A multiplex ligation-dependent probe amplification P095 test kit and array comparative genomic hybridization analysis did not detect genomic imbalance in chromosome 18. Cytogenetic analysis of cultured amniocytes at repeated amniocentesis revealed a karyotype of 47,XY,+i(18)(p10)[3]/46,XY[23]. The pregnancy was carried to 38 weeks of gestation, and a healthy 3120 g male baby was delivered. When examined at 2 months of age, the infant was normal in growth and development, without phenotypic abnormalities. The cord blood had a karyotype of 46,XY. Polymorphic DNA marker analysis excluded uniparental disomy 18. Interphase FISH analysis on uncultured urinary cells showed 9.4% (3/32 cells) mosaicism for tetrasomy 18p.ConclusionThere is cytogenetic discrepancy between amniocytes and cord blood lymphocytes in prenatally detected mosaic tetrasomy 18p. Interphase FISH on uncultured amniocytes has the advantage of rapid confirmation of low-level mosaicism for tetrasomy 18p at amniocentesis.     

Rapid positive confirmation of mosaicism for a small supernumerary marker chromosome as r(8) by interphase fluorescence in situ hybridization,quantitative fluorescent polymerase chain reaction,and array comparative genomic hybridization on uncultured amniocytes in a pregnancy with fetal pyelectasis

ObjectiveThis 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 ResultsA 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].ConclusionPrenatal 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.     

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

ObjectiveWe present prenatal diagnosis of mosaicism for trisomy 7 in a single colony at amniocentesis with a favorable outcome.Case reportA 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.ConclusionMosaicism for trisomy 7 in a single colony at amniocentesis without UPD 7 can be associated with a favorable outcome.     

Mosaic trisomy 2 at amniocentesis: Prenatal diagnosis and molecular genetic analysis

ObjectiveThis study aims at presenting prenatal diagnosis of mosaic trisomy 2 and reviewing the literature.Materials, Methods, and ResultsA 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.ConclusionPrenatal 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.     

Mosaic 46,XY,der(15)t(6;15)(q25.1;p12)/46,XY at amniocentesis in a pregnancy associated with a favorable fetal outcome and postnatal decrease of the aneuploid cell line with the unbalanced translocation

ObjectiveWe present mosaic 46,XY,der(15)t(6;15)(q25.1;p12)/46,XY at amniocentesis in a pregnancy associated with a favorable fetal outcome and postnatal decrease of the aneuploid cell line with the unbalanced translocation.Case reportA 34-year-old primigravid woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 46,XY,add(15)(p12)[17]/46,XY[5]. A second amniocentesis at 19 weeks of gestation revealed a karyotype of 46,XY,der(15)t(6;15)(q25.1;p12)[12]/46,XY[8], and array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed arr arr 6q25.1q27×2-3 with 40% mosaic level. She was referred for genetic counseling. Prenatal ultrasound and the parental karyotypes were normal. A third amniocentesis at 24 weeks of gestation revealed a karyotype of 46,XY,der(15)t(6;15)(q25.1;p12)[23]/46,XY[1], and in uncultured amniocytes, aCGH analysis revealed arr 6q25.1q27×2.5, interphase fluorescence in situ hybridization (FISH) revealed 51% mosaicism (51/100 cells) for partial trisomy 6q and quantitative fluorescence polymerase chain reaction (QF-PCR) analysis determined maternal origin of the aberrant chromosome and excluded uniparental disomy (UPD) 15 and UPD 6. A fourth amniocentesis at 27 weeks of gestation revealed a karyotype of 46,XY,der(15)t(6;15)(q25.1;p12)[21]/46,XY[5], and in uncultured amniocytes, aCGH analysis revealed arr 6q25.1q27×2.46, and interphase FISH revealed 35% mosaicism (35/100 cells) for partial trisomy 6q. At 39 weeks of gestation, a healthy 3028-g male baby was delivered without any phenotypic abnormality. The karyotypes of cord blood, umbilical cord and placenta were 46,XY,der(15)t(6;15)(q25.1;p12)[2]/46,XY,der(15)t(6;15)(q25.1;p12)[29]/46,XY[11] and 46,XY, respectively. When follow-up at age one month, the neonate was phenotypically normal, the peripheral blood had a karyotype of 46,XY (40/40 cells), and FISH analysis on 105 buccal mucosal cells detected five cells with partial trisomy 6q compared with 2% mosaicism (2/100 cells) in the normal control.ConclusionMosaicism for an unbalanced translocation with a normal cell line without UPD at amniocentesis can be a transient and benign condition, and can be associated with a favorable fetal outcome and postnatal decrease of the aneuploid cell line.     

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

ObjectiveWe present prenatal diagnosis of mosaicism for trisomy 12 in a single colony at amniocentesis with a favorable outcome.Case reportA 36-year-old woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 47,XY,+12[1]/46,XY[14]. In 15 colonies of cultured amniocytes, all three cells in one colony had the karyotype of 47,XY,+12, while the rest 14 colonies had the karyotype of 46,XY. The parental karyotypes were normal. Prenatal ultrasound findings were unremarkable. Polymorphic DNA marker analysis using the DNAs extracted from cultured amniocytes and parental bloods excluded uniparental disomy (UPD) 12. At 37 weeks of gestation, a healthy 2,828-g male baby was delivered with no phenotypic abnormality. The cord blood had a karyotype of 46,XY in 40/40 lymphocytes. Postnatal interphase fluorescence in situ hybridization (FISH) analysis on buccal cells and urinary cells revealed normal signals in 72/72 buccal cells, and trisomy 12 signals in 1/47 (2.1%) urinary cells compared with 0% (0/75 cells) of trisomy 12 signals in the normal control.ConclusionMosaicism for trisomy 12 in a single colony at amniocentesis without UPD 12 and fetal ultrasound abnormalities can be associated with a favorable outcome.     

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

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

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

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

Prenatal diagnosis of a distal 3p deletion associated with fetoplacental chromosomal discrepancy and confined placental mosaicism detected by array comparative genomic hybridization

ObjectiveThis study is aimed at prenatal diagnosis of a distal 3p deletion associated with fetoplacental chromosomal discrepancy and confined placental mosaicism, and providing evidence for the limitation of array comparative genomic hybridization (aCGH) on placental tissues for molecular cytogenetic characterization of prenatally detected aneuploidy.Case ReportA 30-year-old woman underwent amniocentesis at 18 weeks of gestation because of maternal anxiety. Results of amniocentesis revealed a distal deletion of chromosome 3p. A malformed female fetus was delivered at 20 weeks of gestation with brachycephaly and facial dysmorphisms, and a cytogenetic analysis of the cord blood revealed a karyotype of 46,XX,del(3)(p26.1),inv(9)(p12q13). A whole-genome aCGH on uncultured cord blood and placental tissue was performed. The aCGH on cord blood revealed a 7.4-Mb deletion at 3p26.3-p26.1. However, the aCGH on placental tissue revealed a 32.42-Mb gene dosage increase at 3p26.1-p22.1 and a 26.28-Mb gene dosage increase at 1p36.33-p36.11 in addition to a 7.4-Mb deletion at 3p26.3-p26.1, indicating confined placental mosaicism for partial trisomy 3p (3p26.1→p22.1) and mosaicism for partial trisomy 1p (1p36.33→p36.11). The 7.4-Mb deleted region of 3p26.3-p26.1 contained the following genes: CHL1, CNTN4, CRBN, LRRN1, and ITPR1.ConclusionFetal tissue and amniocytes offer more reliable resources for aCGH characterization of prenatally detected aneuploidy compared with placental tissues. A molecular cytogenetic evaluation of prenatally detected aneuploidy using placental tissue should raise concerns of confined placental mosaicism and fetoplacental chromosomal discrepancy.     

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

ObjectiveWe present prenatal diagnosis of mosaic isochromosome 20q [i(20q)] at amniocentesis, and we review the literature.Case reportA 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.ConclusionMosaic 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.     

Cytogenetic discrepancy between uncultured amniocytes and cultured amniocytes in mosaic trisomy 15 at amniocentesis

ObjectiveWe present mosaic trisomy 15 at amniocentesis.Materials and methodsA 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.ResultsRepeat 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.ConclusionCytogenetic 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.     

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

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

High-level mosaicism for 45,X in 45,X/46, XY at amniocentesis in a pregnancy with a favorable fetal outcome and cytogenetic discrepancy in various tissues

ObjectiveWe present prenatal diagnosis of high-level mosaicism for 45,X by amniocentesis in a pregnancy with a favorable fetal outcome.Case reportA 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].ConclusionHigh-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.     

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

Objective

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

Prenatal diagnosis of mosaic trisomy 2 associated with abnormal maternal serum screening,oligohydramnios, intrauterine growth restriction,ventricular septal defect,preaxial polydactyly,and facial dysmorphism

ObjectiveTo present prenatal diagnosis of mosaic trisomy 2.Materials and MethodsA 29-year-old woman underwent amniocentesis at 17 weeks of gestation because of abnormal maternal serum screening, and the cytogenetic result was 47,XY,+2[8]/46,XY[22]. She underwent repeated amniocentesis at 19 weeks of gestation. Interphase fluorescence in situ hybridization (FISH), array comparative genomic hybridization (aCGH), and quantitative fluorescent polymerase chain reaction (QF-PCR) were performed on uncultured amniocytes. Ultrasound at 22 weeks of gestation revealed severe oligohydramnios, intrauterine growth restriction, and ventricular septal defect. The pregnancy was terminated at 22 weeks of gestation. Cytogenetic analysis was performed on parental blood, cultured amniocytes, cord blood, skin, liver, lung, umbilical cord, amnion, and placenta. aCGH analysis was performed on cord blood, skin, and liver.ResultsIn the samples of uncultured amniocytes, interphase FISH detected 11.1% (13/117) mosaicism for trisomy 2, aCGH analysis showed the result of arr [hg19] 2p25.3q37.3 (0–242,936,883)×2.46, and QF-PCR excluded uniparental disomy 2. QF-PCR on placenta revealed trisomy 2 derived from maternal meiosis I non-disjunction. Cytogenetic analysis revealed the following results: cultured amniocytes: 46,XY[21 colonies]; cord blood: 46,XY[40 cells]; skin: 46,XY[40 cells]; lung: 46,XY[40 cells]; liver: 47,XY,+2[4 cells]/46,XY[36 cells]; umbilical cord: 47,XY,+2[4 cells]/46,XY[36 cells]; amniotic membrane: 47,XY,+2[20 cells]/46,XY[20 cells]; and placenta: 47,XY,+2[40 cells]. The fetus postnatally manifested facial dysmorphism and preaxial polydactyly of the hand.ConclusionInterphase FISH and aCGH analyses on uncultured amniocytes are useful for rapid confirmation of low-level mosaic trisomy 2 at amniocentesis.     

Prenatal diagnosis and molecular cytogenetic characterization of de novo distal 5p deletion and distal 22q duplication

ObjectiveWe present prenatal diagnosis and molecular cytogenetic characterization of de novo distal 5p deletion and distal 22q duplication.Case reportA 34-year-old woman was underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a derivative chromosome 5 [der(5)] with an abnormal distal 5p segment of unknown origin. The parental karyotypes were normal. Array comparative genomic hybridization (aCGH) analysis was performed on the cultured amniocytes, and the result was arr 5p15.33p13.3 (22,149–29,760,922) × 1.0, arr 22q13.2q13.33 (42, 192, 065–51,178,264) × 3.0 [GRCh37 (hg19)] with a 29.739-Mb deletion of 5p15.33-p13.3 encompassing 55 [Online Mendelian Inheritance in Man (OMIM)] genes including TPPP, TERT, SRD5A1, SEMA5A and CTNND2, and an 8.986-Mb duplication of 22q13.2-q13.33 encompassing 82 OMIM genes including TRMU, SCO2, TYMP, CPT1B and SHANK3. The fetal karyotype was 46,XY,der(5)t(5; 22)(p13.3; q13.2)dn. The pregnancy was subsequently terminated, and a malformed fetus was delivered with facial dysmorphism. Postnatal polymorphic DNA marker analysis confirmed a maternal origin of the aberrant chromosome 5.ConclusionaCGH and polymorphic DNA marker analyses can determine the nature and parental origin of the de novo chromosome aberration, and the information acquired is useful for genetic counseling.     

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

ObjectiveWe 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 reportA 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.ConclusionCytogenetic 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.     

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

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