We present 45,X/46,XX at amniocentesis associated with cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes and in different amniocenteses and a favorable fetal outcome with ...a normal karyotype at birth.
A 35-year-old, gravida 3, para 2, woman underwent amniocentesis at 20 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 45,X11/46,XX108, consistent with 9.2% mosaicism for 45,X. Prenatal ultrasound findings were unremarkable. She was referred for genetic counseling at 25 weeks of gestation, and repeat amniocentesis at 26 weeks of gestation revealed a karyotype of 45,X4/46,XX16, consistent with 20% mosaicism for 45,X. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes using SurePrint G3 Unrestricted CGH ISCA v2, 8 × 60K (Agilent Technologies, Santa Clara, CA, USA) revealed arr (1–22, X) × 2, Y × 0 with no genomic imbalance. The woman was advised to continue pregnancy, and at 38 weeks of gestation, a healthy 3140-g female baby was delivered with no phenotypic abnormalities. The cord blood had a karyotype of 46,XX (40/40 cells). When follow-up at age two months, the neonate had normal development and a normal karyotype.
Confirmation of 45,X/46,XX at amniocentesis should include conventional cytogenetic analysis and karyotyping on cultured amniocytes, and sole molecular analysis on uncultured amniocytes may miss the diagnosis of 45,X/46,XX.
We present mosaicism for a 15q11.2 microduplication with a normal euploid cell line at amniocentesis in a pregnancy with a favorable fetal outcome and postnatal decrease of the aneuploid cell line ...with the microduplication.
A 35-year-old, primigravid woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 46,XY. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed 33.76% mosaicism for a 15q11.2 microduplication. She was referred for genetic counseling. Repeat amniocentesis was performed at 23 weeks of gestation, and the karyotype was 46,XY. Simultaneous aCGH analysis on the DNA extracted from uncultured amniocytes revealed the result of arr GRCh37 (hg19) 15q11.2 (23, 889, 686–25,514,125) × 2.45, consistent with a mosaic 1.624-Mb microduplication with the mosaic level of 40%–45% (log2 ratio = 0.28) encompassing nine OMIM genes of MAGEL2, NDN, PWRN2, PWRN1, NPAP1, SNRPN, SNHG14, SNORD116-1 and SNORD115-1. Interphase fluorescence in situ hybridization (FISH) analysis on 100 uncultured amniocytes detected a 15q11.2 duplication in 19 cells, consistent with 19% (19/100 cells) mosaic15q11.2 duplication. Polymorphic DNA marker analysis excluded uniparental disomy (UPD) 15. Prenatal ultrasound findings were unremarkable. She was advised to continue the pregnancy, and a 3865-g phenotypically normal male baby was delivered. aCGH analysis on the DNA extracted from cord blood at birth and buccal mucosal cells at age four months revealed arr (1–22) × 2, X × 1, Y × 1 and detected no genomic imbalance in all samples. Interphase FISH analysis on 104 buccal mucosal cells at age four months detected four cells (4/104 = 4%) with a 15q11.2 duplication, compared with 0% (0/102 cells) in the normal control. The neonate was normal in the development.
Mosaicism for a 15q11.2 microduplication at amniocentesis with a normal euploid cell line can be a benign condition and associated with a favorable fetal outcome and postnatal decrease of the aneuploid cell line with the microduplication.
We present prenatal diagnosis and perinatal findings of 17q12 microdeletion encompassing HNF1B in a fetus with bilateral hyperechogenic kidneys on fetal ultrasound and mild renal abnormality after ...birth, and a review of the literature.
A 36-year-old, primigravid woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes showed a de novo 1.38-Mb 17q12 microdeletion encompassing LHX1 and HNF1B. The parents did not have such a microdeletion. Prenatal ultrasound showed bilateral hyperechogenic kidneys with normal corticomedullary (CM) differentiation. The parents elected to continue the pregnancy, and a grossly normal 3180-g male baby was delivered at 39 weeks of gestation. aCGH analysis on the cord blood DNA revealed arr GRCh37 (hg19) 17q12 (34,856,055-36,248,918) × 1.0 with a 1.393-Mb microdeletion encompassing the genes of MYO19, PIGW, GGNBP2, DHRS11, MRM1, LHX1, AATF, ACACA, TADA2A, DUSP14, SYNRG, DDX52 and HNF1B. When follow-up at age 2 years and 4 months, the renal ultrasound revealed bilateral increased renal echogenicity with normal CM differentiation and small left renal cysts. The blood test revealed BUN = 28 mg/dL (normal: 5-18 mg/dL) and creatinine = 0.5 mg/dL (normal: 0.2-0.4 mg/dL).
17q12 microdeletion encompassing LHX1 and HNF1B at prenatal diagnosis may present variable clinical spectrum with bilateral hyperechogenic kidneys on fetal ultrasound and mild renal abnormality after birth. Prenatal diagnosis of fetal hyperechogenic kidneys should raise a suspicion of 17q12 microdeletion syndrome.
We present mosaicism for a 12p12.1p12.2 microdeletion with a normal euploid cell line at amniocentesis in a pregnancy with a favorable outcome and postnatal decrease of the aneuploid cell line with ...microdeletion.
A 35-year-old woman, gravida 2, para 1, underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed mosaic 46,XY,del (12) (p11.2p12), and array comparative genomic hybridization (aCGH) revealed arr Xp22.31 × 2 mat, 12p12.2p12.1 × 1 0.36dn with a 4.15-Mb 36% mosaicism for a 12p12.1p12.2 microdeletion. At 22 weeks of gestation, she underwent cord blood sampling of which aCGH revealed arr Xp22.31 × 2 mat, 12p12.2p12.1 × 1 0.34dn with a 4.24-Mb 34% mosaicism for a 12p12.1p12.2 microdeletion. Prenatal ultrasound findings were unremarkable. She was referred for genetic counseling, and continuing pregnancy was advised. A 2990-g male baby was delivered at 38 weeks of gestation with no phenotypic abnormality. When follow-up at age 1½ months, the neonate was phenotypically normal. The karyotype of peripheral blood was 46,XY. aCGH analysis on the DNA extracted from peripheral blood revealed the result of arr 12p12.1p12.2 (20, 367, 240–24,489,386) × 1.87, arr Xp22.31 (6,488,721–8,097,511) × 2.0 GRCh37 (hg19) with 10–15% (log2 ratio = 0.1) mosaicism for a 4.122-Mb 12p12.1-p12.2 microdeletion encompassing 17 OMIM genes of PDE3A, SLCO1C1, SLCO1B3, SLCO1B1, IAPP, PYROXD1, RECQL, GOLT1B, SPX, GYS2, LDHB, KCNJ8, ABCCP, CMAS, C2CD5, ETNK1 and SOX5 and a 1.609-Mb Xp22.31 duplication encompassing two OMIM genes of STS and VCX. Interphase fluorescence in situ hybridization (FISH) analysis on 104 buccal mucosal cells using 12p12.1-specific probe showed 17% (18/104 cells) mosaicism for a 12p12.1 deletion. Polymorphic DNA marker analysis on the DNA extracted from proband's blood and parental bloods determined a paternal origin of the mosaic 12p12.1 deletion.
Mosaicism for a 12p12.1p12.2 microdeletion at amniocentesis with a normal euploid cell line can be a benign condition in association with a favorable fetal outcome and postnatal decrease of the aneuploid cell line with microdeletion.
We present low-level mosaic trisomy 21 at amniocentesis and cordocentesis in a pregnancy associated with a favorable fetal outcome.
A 26-year-old, primigravid woman underwent amniocentesis at 17 ...weeks of gestation because of positive non-invasive prenatal testing (NIPT) for trisomy 21 at 16 weeks of gestation. Amniocentesis revealed a karyotype of 47,XX,+213/46,XX17, and multiplex ligation-dependent probe amplification (MLPA) on uncultured amniocytes revealed rsa X(P095) × 2, (13, 18, 21) × 2. She underwent cordocentesis (cord blood sampling) at 21 weeks of gestation which revealed a karyotype of 47,XX,+212/46,XX48. At 27 weeks of gestation, she was referred to our hospital for genetic counseling, and repeat amniocentesis revealed a karyotype of 46,XX in 20/20 colonies. Quantitative fluorescent polymerase chain reaction (QF-PCR) analysis on the DNA extracted from uncultured amniocytes and parental bloods excluded uniparental disomy (UPD) 21. Array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed arr (1–22,X) × 2, Y × 0 with no genomic imbalance. Interphase fluorescence in situ hybridization (FISH) analysis on 104 uncultured amniocytes detected one cell (1/104 = 0.9%) with trisomy 21, while the rest cells were disomy 21, compared with 0% (0/100) in the normal control. The woman was encouraged to continue the pregnancy. The pregnancy was carried to 38 weeks of gestation, and a 2771-g female baby was delivered no phenotypic abnormality. aCGH analysis on the cord blood showed arr (1–22,X) × 2, Y × 0 with no genomic imbalance. The umbilical cord had a karyotype of 47,XX,+213/46,XX37. The placenta had a karyotype of 46,XX. When follow-up at age 3½ months, the neonate was phenotypically normal and had normal development. The peripheral blood had a karyotype of 46,XX in 40/40 cells. Interphase FISH analysis on buccal mucosal cells detected normal disomy 21 cells in 100/100 cells.
Low-level mosaic trisomy 21 at amniocentesis and cordocentesis in the second trimester can be associated with perinatal progressive decrease of the trisomy 21 cell line and a favorable fetal outcome.
We present high-level mosaic trisomy 21 at amniocentesis in a pregnancy associated with positive non-invasive prenatal testing (NIPT) for trisomy 21, prenatal progressive decrease of the trisomy ...21 cell line, acute fatty liver of pregnancy and intrauterine fetal death (IUFD) in late gestation.
A 32-year-old, primigravid woman underwent amniocentesis at 17 weeks of gestation because of positive NIPT for trisomy 21 at 12 weeks of gestation. This pregnancy was conceived by in vitro fertilization. She did not have obesity, diabetes mellitus, hepatic biliary disorders and preeclampsia. Amniocentesis revealed a karyotype of 47,XY,+2110/46,XY11, and array comparative genomic hybridization (aCGH) analysis on uncultured amniocytes revealed the result of arr (21) × 2–3. She was referred for genetic counseling, and repeat amniocentesis performed at 21 weeks of gestation revealed the karyotype of 47,XY,+2110/46,XY28. The parental karyotypes and fetal ultrasound findings were normal. Simultaneous molecular analysis on uncultured amniocytes showed no uniparental disomy 21, but a maternal origin of trisomy 21 by quantitative fluorescent polymerase chain reaction (QF-PCR) and the result of arr 21q11.2q22.3 × 2.5 by aCGH analysis. At 27 weeks of gestation, she underwent a third amniocentesis, of which conventional cytogenetic analysis revealed the result of 47,XY,+215/46,XY17 in cultured amniocytes, and aCGH analysis revealed arr 21q11.2q22.3 × 2.48, and interphase fluorescence in situ hybridization (FISH) analysis revealed 39% (39/100 cells) mosaicism fro trisomy 21 in uncultured amniocytes. At 36 weeks of gestation, the woman suffered from a sudden onset of acute fatty liver and IUFD. A 3522-g male baby was delivered without Down syndrome phenotype. The umbilical cord had a karyotype of 47,XY,+2110/46,XY30. aCGH analysis on the skin and placenta showed arr 21q11.2q22.3 × 2.73 and arr 21q11.2q22.3 × 2.75, respectively. QF-PCR analysis of umbilical cord, placenta and skin showed a maternal origin of trisomy 21.
High-level mosaic trisomy 21 at amniocentesis can be associated with prenatal progressive decrease of the trisomy 21 cell line in cultured amniocytes and perinatal fetal mortality and maternal morbidity.
We present 45,X/46,XX at the first amniocentesis, and 45,X/47,XXX/46,XX at the repeat amniocentesis and at birth in a pregnancy associated with a favorable fetal outcome, perinatal progressive ...decrease of the 45,X cell line and cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes.
A 43-year-old, gravida 3, para 1, woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 45,X4/46,XX20. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed arr (X) × 3 0.24, consistent with 24% mosaicism for triple X. Repeat amniocentesis at 20 weeks of gestation revealed the result of 45,X17/47,XXX8/46,XX121. She was referred for genetic counseling, and the third amniocentesis performed at 30 weeks of gestation revealed the result of 45,X3/47,XXX2/46,XX16. The mother had a karyotype of 46,XX. aCGH analysis on the DNA extracted from uncultured amniocytes showed arr Xp22.33q28 × 2.2 (log2 ratio = 0.15), consistent with 20% mosaicism for triple X. Interphase fluorescence in situ hybridization (FISH) analysis on 100 uncultured amniocytes showed that 11 cells (11%) were monosomy X, seven cells (7%) were triple X, and the others were disomy X. At 39 weeks of gestation, a 3,620-g phenotypically normal female baby was delivered without any phenotypic abnormality. The karyotypes of cord blood, umbilical cord and placenta were 47,XXX7/45,X1/46,XX32, 47,XXX13/46,XX27 and 47,XXX2/46,XX38, respectively. When follow-up at age one month, the neonate was phenotypically normal, and FISH analysis on 106 buccal mucosal cells showed that eight cells (7.5%) were monosomy X, seven cells (6.6%) were triple X, and the others were disomy X.
Mosaic 45,X/46,XX at amniocentesis may be in fact mosaic 45,X/47,XXX/46,XX and can be associated with a favorable fetal outcome and perinatal progressive decrease of the 45,X cell line.
We present perinatal detection of disomy X cell line by fluorescence in situ hybridization (FISH) in a pregnancy with 45,X/47,XXX at amniocentesis, cytogenetic discrepancy in various tissues and a ...favorable outcome.
A 34-year-old, gravida 3, para 1, woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 45,X22/47,XXX10. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed the result of arr (X) × 1–2, (1–22) × 2, consistent with 32% mosaicism for monosomy X. She was referred for genetic counseling at 19 weeks of gestation. Prenatal ultrasound findings and parental karyotypes were normal. Repeat amniocentesis at 29 weeks of gestation revealed a karyotype of 45,X36/47,XXX4 (Fig. 1) in cultured amniocytes. Simultaneous molecular analysis on uncultured amniocytes revealed the result of arr (1–22) × 2, Y × 0 by aCGH with no genomic imbalance, and 15% (15/100 cells) mosaicism for disomy X, 61% (61/100 cells) mosaicism for monosomy X and 24% (24/100 cells) mosaicism for triple X by interphase fluorescence in situ hybridization (FISH) analysis. The pregnancy was encouraged to continue and at 37 weeks of gestation, a 2834-g phenotypically normal female baby was delivered. The karyotypes of cord blood, umbilical cord and placenta were 45,X33/47,XXX7, 45,X30/47,XXX10 and 47,XXX38/45,X2, respectively. When follow-up at age three months, the neonate was normal in development. FISH analysis on 99 buccal mucosal cells showed 49% (48/99 cells) mosaicism for monosomy X, 8% (8/99 cells) mosaicism for triple X and 43% (42/99 cells) mosaicism for disomy X (Fig. 2). Peripheral blood had a karyotype of 45,X38/47,XXX2.
45,X/47,XXX at amniocentesis may detect disomy X cell line by FISH analysis and can be associated with postnatal progressive decrease of the aneuploid cell lines, increase of the disomy X cell line and a favorable outcome.
We present incidental detection of familial 8p23.2 microduplication encompassing CSMD1 associated with mosaic 46,XY,t(7;8)(q31.2;p23.1)/46,XY at amniocentesis in a pregnancy with no apparent ...phenotypic abnormality and a favorable outcome.
A 38-year-old, gravida 2, para 1, phenotypically normal woman underwent amniocentesis at 19 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 46,XY,t(7;8)(q31.2;p23.1)2/46,XY20. The parental karyotypes were normal. Array comparative genomic hybridization (aCGH) analysis on the DNA extracted from cultured amniocytes and parental bloods revealed the result of a 2.178-Mb 8p23.2 microduplication encompassing CSMD1, or arr 8p23.2 (3,070,237–5,248,586) × 3.0 GRCh37 (hg19) in the fetus and the mother. The father did not have such a microduplicaiton. Prenatal ultrasound findings were unremarkable. At 38 weeks of gestation, a 2880-g phenotypically normal male baby was delivered. All the cord blood, umbilical cord and placenta had the karyotype of 46.XY. When follow-up at age six months, the neonate was normal in phenotype and development.
Mosaicism for a balanced reciprocal translocation with a euploid cell line can be a transient and benign condition. Familial 8p23.2 microduplication encompassing CSMD1 can be associated with a favorable outcome.
We present low-level mosaic trisomy 21 at amniocentesis in a pregnancy with a favorable fetal outcome.
A 38-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,XY,+214/46,XY34. Prenatal ultrasound findings were normal. At 27 weeks of gestation, she was referred for genetic counseling, and the cultured amniocytes had a karyotype of 47,XY,+212/46,XY26. Quantitative fluorescent polymerase chain reaction (QF-PCR) analysis on the DNA extracted from uncultured amniocytes and parental bloods excluded uniparental disomy (UPD) 21. Interphase fluorescence in situ hybridization (FISH) analysis on uncultured amniocytes revealed 30% (30/100 cells) mosaicism for trisomy 21. Array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed the result of arr 21q11.2q22.3 × 2.25, consistent with 20%–30% mosaicism for trisomy 21. The parental karyotypes were normal. The woman was advised to continue the pregnancy, and a 3510-g phenotypically normal male baby was delivered at 39 weeks of gestation. Cytogenetic analysis of the cord blood, umbilical cord and placenta revealed the karyotypes of 47,XY,+211/46,XY39, 47,XY,+212/46,XY38 and 46,XY in 40/40 cells, respectively. When follow-up at age 1 year and 2 months, the neonate was normal in phenotype and development. The peripheral blood had a karyotype of 46,XY in 40/40 cells, and interphase FISH analysis on uncultured buccal mucosal cells showed 6.4% (7/109 cells) mosaicism for trisomy 21.
Low-level mosaic trisomy 21 at amniocentesis can be associated with cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes, perinatal progressive decrease of the trisomy 21 cell line and a favorable fetal outcome.
