ABSTRACT
OBJECTIVE: We present mosaic distal 9p deletion at prenatal diagnosis in a pregnancy associated with a favorable fetal outcome. CASE REPORT: A 34-year-old, primigravid woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 46,XY, del(9)(p23)[8]/46,XY[17]. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes showed 43% mosaicism for the 9p24.3p23 deletion. Prenatal ultrasound suspected hypospadias and echogenic bowel. At 23 weeks of gestation, she was referred for genetic counseling, and repeat amniocentesis revealed a karyotype of 46,XY,del(9)(p23)[10]/46,XY[10]. The parental karyotypes were normal. Molecular genetic analysis on uncultured amniocytes revealed no uniparental disomy (UPD) 9 by quantitative fluorescence polymerase chain reaction (QF-PCR) and arr 9p24.3p23 × 1.55 (40%-50% mosaicism) by aCGH. At 27 weeks of gestation, she underwent the third amniocentesis which revealed a karyotype of 46,XY,del(9)(p23)[6]/46,XY[14]. Simultaneous aCGH analysis on the DNA extracted from uncultured amniocytes revealed the result of arr 9p24.3p23 (35% mosaicism). Prenatal ultrasound was normal. She was advised to continue the pregnancy, and a 3020-g phenotypically normal male baby was delivered at 41 weeks of gestation. At birth, the karyotypes of cord blood, umbilical cord and placenta were 46,XY,del(9)(p23)[7]/46,XY[37], 46,XY,del(9)(p23)[17]/46,XY[23] and 46,XY in 40/40 cells, respectively. When follow-up at age three months, the neonate was normal in phenotype and development. The peripheral blood had a karyotype of 46,XY,del(9)(p23)[3]/46,XY[37], and interphase fluorescence in situ hybridization (FISH) analysis on buccal mucosal cells showed 13% (13/102 cells) mosaicism for the distal 9p deletion. CONCLUSION: Mosaic distal 9p deletion with a normal cell line at prenatal diagnosis can be associated with a favorable fetal outcome and perinatal progressive decrease of the aneuploid cell line.
Subject(s)
Amniocentesis , Chromosome Deletion , Chromosomes, Human, Pair 9 , Mosaicism , Humans , Pregnancy , Female , Adult , Mosaicism/embryology , Chromosomes, Human, Pair 9/genetics , Comparative Genomic Hybridization , Infant, Newborn , Male , Aneuploidy , Karyotyping , Pregnancy Outcome/geneticsABSTRACT
OBJECTIVE: We present low-level mosaic trisomy at amniocentesis in a pregnancy associated with cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes, perinatal progressive decrease of the trisomy 7 cell line and a favorable fetal outcome. CASE REPORT: A 40-year-old, primigravid woman underwent amniocentesis at 16 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 46,XY in cultured amniocytes. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed the result of arr (7) × 2-3, (X,Y) × 1, consistent with 24% mosaicism for trisomy 7. Polymorphic DNA marker analysis on the DNA extracted from the uncultured amniocytes and parental bloods excluded uniparental disomy (UPD) 7. Prenatal ultrasound findings were normal. She was referred for genetic counseling at 19 weeks of gestation. No repeat amniocentesis was suggested, and continuing the pregnancy was advised. At 22 weeks of gestation, the result of soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) = 6.1 (normal < 38). She did not have preeclampsia. At 39 weeks of gestation, a 3346-g male baby was delivered without any phenotypic abnormality. aCGH analysis on the DNA extracted from cord blood and placenta revealed the result of arr (1-22) × 2, (X,Y) × 1 with no genomic imbalance in all tissues. When follow-up at age three months, the baby was normal in development and phenotype. The peripheral blood had a karyotype of 46,XY, and interphase fluorescence in situ hybridization (FISH) analysis using the bacterial artificial chromosome (BAC) probes of chromosome 7 showed disomy 7 cells in all 102/102 cells. CONCLUSION: Low-level mosaic trisomy 7 at amniocentesis can be associated with cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes, perinatal progressive decrease of the trisomy 7 cell line and a favorable fetal outcome.
Subject(s)
Amniocentesis , Chromosomes, Human, Pair 7 , Comparative Genomic Hybridization , Mosaicism , Trisomy , Uniparental Disomy , Humans , Pregnancy , Female , Mosaicism/embryology , Trisomy/diagnosis , Trisomy/genetics , Adult , Chromosomes, Human, Pair 7/genetics , Uniparental Disomy/diagnosis , Uniparental Disomy/genetics , Infant, Newborn , Cell Line , Cells, Cultured , Pregnancy Outcome/geneticsABSTRACT
OBJECTIVE: We present prenatal diagnosis of familial 3p26.3p25.3 deletion in a pregnancy associated with a favorable fetal outcome and asymptomatic carrier parent and family members in three generations. CASE REPORT: A 35-year-old, gravida 2, para 1, woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age and the carrier of distal 3p deletion. She was phenotypically normal, and there was no family history of congenital anomalies. Amniocentesis revealed a karyotype of 46,XY,del(3)(p26.1). Repeat amniocentesis at 21 weeks of gestation revealed a karyotype of 46,XY,del(3)(p25.3). Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes showed the result of arr 3p26.3p25.3 (117,735-8,709,972) × 1.0 [GRCh37 (hg19)] with an 8.59-Mb deletion of 3p26.3p25.3 encompassing 14 OMIM genes of CHL1, CNTN6, CNTN4, IL5RA, TRNT1, CRBN, SETMAR, SUMF1, ITPR1, BHLHE40, ARL8B, GRM7, LMCD1 and SSUH2. Cytogenetic analysis of parental bloods revealed a karyotype of 46,XX,del (3) (p25.3) in the mother and 46,XY in the father. The woman's 69-year-old mother and her 2-year-old elder son carried the same aberrant chromosome of 3p25.3âp26.3 deletion by conventional cytogenetic analysis but manifested no phenotypic abnormality. aCGH analysis of the peripheral bloods showed that the woman's mother and her elder son had the same 8.59-Mb deletion of 3p26.3p25.3. The woman was advised to continue the pregnancy. At 39 weeks of gestation, a 3040-g healthy male baby was delivered. When follow-up at age 2½ years, the neonate was normal in development and showed no apparent phenotypic abnormality. CONCLUSION: Distal 3p deletion of 3p26.3p25.3 involving the OMIM genes from CHL1 to SSUH2 can be associated with no apparent phenotypic abnormality.
Subject(s)
Amniocentesis , Chromosome Deletion , Chromosomes, Human, Pair 3 , Comparative Genomic Hybridization , Pedigree , Humans , Female , Pregnancy , Chromosomes, Human, Pair 3/genetics , Adult , Male , Heterozygote , Infant, NewbornABSTRACT
OBJECTIVE: We present prenatal diagnosis of de novo 10p12.1p11.23 microdeletion encompassing the WAC gene in a fetus associated with bilateral hydronephrosis on prenatal ultrasound. CASE REPORT: A 40-year-old, gravida 2, para 1, woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 46,XY. Level II ultrasound at 22 weeks of gestation revealed bilateral hydronephrosis and right clubfoot. At 23 weeks of gestation, repeat amniocentesis revealed the result of arr [GRCh37] 10p12.1p11.23 (26,182,512-29,826,276) × 1 dn with a 3.6-Mb microdeletion of 10p12.1p11.23 encompassing the genes of MYO3A, GAD2, APBB1IP, PDSS1, ABI1, ANKRD26, YME1L1, MASTL, ACBD5, PTCHD3, RAB18, MKX, ODAD2, MPP7, WAC and BAMBI. The pregnancy was subsequently terminated, and a malformed fetus was delivered with facial dysmorphism of low-set ears, broad forehead and flat nasal bridge. Array comparative genomic hybridization (aCGH) analysis of umbilical cord confirmed a 3.6-Mb 10p12.1p11.23 microdeletion encompassing WAC. CONCLUSION: Application of aCGH is useful in the pregnancy with a normal fetal karyotype and abnormal fetal ultrasound.
Subject(s)
Amniocentesis , Chromosome Deletion , Chromosomes, Human, Pair 10 , Clubfoot , Hydronephrosis , Ultrasonography, Prenatal , Humans , Female , Clubfoot/genetics , Clubfoot/diagnostic imaging , Pregnancy , Adult , Hydronephrosis/genetics , Hydronephrosis/diagnostic imaging , Chromosomes, Human, Pair 10/genetics , Abortion, InducedABSTRACT
OBJECTIVE: We present low-level mosaic trisomy 21 at amniocentesis and cordocentesis in a pregnancy associated with a favorable fetal outcome. CASE REPORT: 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,+21[3]/46,XX[17], 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,+21[2]/46,XX[48]. 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,+21[3]/46,XX[37]. 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. CONCLUSION: 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.
Subject(s)
Amniocentesis , Cordocentesis , Down Syndrome , Mosaicism , Pregnancy Trimester, Second , Humans , Female , Pregnancy , Adult , Down Syndrome/diagnosis , Down Syndrome/genetics , Mosaicism/embryology , Infant, Newborn , Live Birth/genetics , Noninvasive Prenatal Testing/methods , Karyotyping , Pregnancy OutcomeABSTRACT
OBJECTIVE: We present low-level mosaic trisomy 21 at amniocentesis in a pregnancy with a favorable fetal outcome. CASE REPORT: 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,+21[4]/46,XY[34]. 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,+21[2]/46,XY[26]. 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,+21[1]/46,XY[39], 47,XY,+21[2]/46,XY[38] 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. CONCLUSION: Low-level mosaic trisomy 21 at amniocentesis can be associated with cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes, perinatal progressive decrease of the trisomy 21 cell line and a favorable fetal outcome.
Subject(s)
Amniocentesis , Comparative Genomic Hybridization , Down Syndrome , In Situ Hybridization, Fluorescence , Mosaicism , Humans , Pregnancy , Female , Mosaicism/embryology , Adult , Down Syndrome/genetics , Down Syndrome/diagnosis , Infant, Newborn , Cell Line , Cells, Cultured , Karyotyping/methods , Amnion/cytology , MaleABSTRACT
OBJECTIVE: We present mosaic distal 10q deletion at prenatal diagnosis in a pregnancy associated with a favorable fetal outcome. CASE REPORT: A 40-year-old, gravida 2, para 0, woman underwent amniocentesis at 16 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 46,XY, del(10) (q26.13)[6]/46,XY[17]. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes showed 35% mosaicism for the 10q26.13q26.3 deletion. At 22 weeks of gestation, she underwent cordocentesis which revealed a karyotype of 46,XY,del(10) (q26.13)[16]/46,XY[24]. Prenatal ultrasound findings were normal. At 24 weeks of gestation, she was referred for genetic counseling, and repeat amniocentesis revealed a karyotype of 46,XY,del(10) (q26.13)[4]/46,XY[22]. The parental karyotypes were normal. Molecular genetic analysis on uncultured amniocytes revealed no uniparental disomy (UPD) 10 by quantitative fluorescence polymerase chain reaction (QF-PCR), arr 10q26.13q26.3 × 1.6 (40% mosaicism) by aCGH, and 29.8% (31/104 cells) mosaicism for the distal 10q deletion by interphase fluorescence in situ hybridization (FISH). The woman was advised to continue the pregnancy, and a phenotypically normal 2,900-g male baby was delivered at 39 weeks of gestation. The cord blood had a karyotype of 46,XY,del(10) (q26.13)[6]/46,XY[34], and both the umbilical cord and the placenta had the karyotype of 46,XY. When follow-up at age four months, the neonate was normal in phenotype and development. The peripheral blood had a karyotype of 46,XY,del(10) (q26.13)[5]/46,XY[35], and interphase FISH analysis on buccal mucosal cells showed 8% (8/102 cells) mosaicism for distal 10q deletion. CONCLUSION: Mosaic distal 10q deletion with a normal cell line at prenatal diagnosis can be associated with a favorable fetal outcome and perinatal progressive decrease of the aneuploid cell line.
Subject(s)
Amniocentesis , Comparative Genomic Hybridization , Cordocentesis , Mosaicism , Humans , Pregnancy , Female , Mosaicism/embryology , Adult , Chromosomes, Human, Pair 10/genetics , Chromosome Deletion , Infant, Newborn , Aneuploidy , KaryotypingABSTRACT
OBJECTIVE: We present perinatal imaging findings of a fetus with Pfeiffer syndrome and a heterozygous c.1019A>G, p.Tyr340Cys (Y340C) mutation in FGFR2 presenting a cloverleaf skull, craniosynostosis and short limbs on prenatal ultrasound mimicking thanatophoric dysplasia type II (TD2). CASE REPORT: A 37-year-old, gravida 2, para 1, woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 46,XY. However, craniofacial anomaly was found on prenatal ultrasound at 21 weeks of gestation, which showed a cloverleaf skull with severe craniosynostosis and relatively short straight long bones. Fetal magnetic resonance imaging (MRI) analysis at 22 weeks of gestation showed a cloverleaf skull, proptosis and relatively shallowing of the sylvian fissures. Prenatal ultrasound at 24 weeks of gestation showed a fetus with a cloverleaf skull with a biparietal diameter (BPD) of 6.16 cm (equivalent to 24 weeks), an abdominal circumference (AC) of 18.89 cm (equivalent to 24 weeks) and a femur length (FL) of 3.65 cm (equivalent to 21 weeks). A tentative diagnosis of TD2 was made. The pregnancy was subsequently terminated, and a 928-g malformed fetus was delivered with severe craniosynostosis, proptosis, midface retrusion, a cloverleaf skull, broad thumbs and broad big toes. The broad thumbs were medially deviated. Whole body X-ray showed a cloverleaf skull and straight long bones. However, molecular analysis of FGFR3 on the fetus revealed no mutation in the target regions. Subsequent whole exome sequencing (WES) on the DNA extracted from umbilical cord revealed a heterozygous c.1019A>G, p.Tyr340Cys (Y340C) mutation in the FGFR2 gene. CONCLUSION: Fetuses with a Y340C mutation in FGFR2 may present a cloverleaf skull on prenatal ultrasound, and WES is useful for a rapid differential diagnosis of Pfeiffer syndrome from TD2 under such a circumstance.
Subject(s)
Acrocephalosyndactylia , Craniosynostoses , Receptor, Fibroblast Growth Factor, Type 2 , Thanatophoric Dysplasia , Ultrasonography, Prenatal , Humans , Female , Acrocephalosyndactylia/genetics , Acrocephalosyndactylia/diagnostic imaging , Acrocephalosyndactylia/diagnosis , Pregnancy , Adult , Receptor, Fibroblast Growth Factor, Type 2/genetics , Craniosynostoses/genetics , Craniosynostoses/diagnostic imaging , Craniosynostoses/diagnosis , Thanatophoric Dysplasia/genetics , Thanatophoric Dysplasia/diagnostic imaging , Mutation , Diagnosis, Differential , Magnetic Resonance Imaging , Heterozygote , Infant, Newborn , Skull/diagnostic imaging , Skull/abnormalities , Skull/embryologyABSTRACT
OBJECTIVE: 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. CASE REPORT: 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,XY[20]. 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. CONCLUSION: 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.
Subject(s)
Amniocentesis , Mosaicism , Pregnancy , Infant, Newborn , Female , Male , Humans , Infant , Adult , Comparative Genomic Hybridization , Karyotyping , Karyotype , Trisomy , Membrane Proteins , Tumor Suppressor ProteinsABSTRACT
OBJECTIVE: 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. CASE REPORT: 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). CONCLUSION: 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.
Subject(s)
17-Hydroxysteroid Dehydrogenases , Chromosome Deletion , Prenatal Diagnosis , Urogenital Abnormalities , Adult , Child, Preschool , Female , Humans , Male , Pregnancy , Amniocentesis , Apoptosis Regulatory Proteins , Comparative Genomic Hybridization , DNA , Fetus , Hepatocyte Nuclear Factor 1-beta/genetics , Kidney/diagnostic imaging , Repressor Proteins/genetics , Ultrasonography, PrenatalABSTRACT
OBJECTIVE: We present low-level mosaic trisomy 21 at amniocentesis in a pregnancy associated with cytogenetic discrepancy in various tissues, perinatal progressive decrease of the trisomy 21 cell line and a favorable fetal outcome. CASE REPORT: A 36-year-old, gravida 2, para 1, woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age, and the result was 47,XY,+21 [8]/46,XY [26]. Prenatal ultrasound findings were unremarkable. She was referred for genetic counseling, and repeat amniocentesis performed at 23 weeks of gestation revealed the result of 47,XY,+21 [3]/46,XY [21]. The parental karyotypes were normal. At repeat amniocentesis, quantitative fluorescent polymerase chain reaction (QF-PCR) analysis using the DNA extracted from uncultured amniocytes and parental bloods excluded uniparental disomy (UPD) 21, array comparative genomic hybridization (aCGH) analysis on uncultured amniocytes revealed the result of arr 21q11.2q22.3 × 2.4, consistent with 40% mosaicism for trisomy 21, and fluorescence in situ hybridization (FISH) analysis on uncultured amniocytes revealed 67% (67/100 cells) mosaicism for trisomy 21. The woman was advised to continue the pregnancy, and a 1370-g male baby was delivered prematurely at 29 weeks of gestation without phenotypic abnormalities. The karyotypes of umbilical cord and placenta were 47,XY,+21 [13]/46,XY [27] and 47,XY,+21 [40], respectively. QF-PCR determined maternal origin of the extra chromosome 21 of trisomy 21 in the placenta. When follow-up at age 8½ months, the neonate was normal in appearance and development. The peripheral blood had a karyotype of 47,XY,+21 [1]/46,XY [39], and FISH analysis on buccal mucosal cells showed 9.7% (11/113 cells) mosaicism for trisomy 21, compared with 2% (2/100 cells) in the normal control. CONCLUSION: Low-level mosaic trisomy 21 at amniocentesis can be associated with cytogenetic discrepancy in various tissues, perinatal progressive decrease of the trisomy 21 cell line and a favorable fetal outcome.
Subject(s)
Amniocentesis , Down Syndrome , Pregnancy , Infant, Newborn , Female , Male , Humans , Child , Adult , Down Syndrome/diagnosis , Down Syndrome/genetics , Mosaicism , Chromosomes, Human, Pair 21/genetics , Comparative Genomic Hybridization , In Situ Hybridization, Fluorescence , Trisomy , Karyotyping , Cell Line , Cytogenetic AnalysisABSTRACT
OBJECTIVE: 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. CASE REPORT: 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,+21[10]/46,XY[11], 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,+21[10]/46,XY[28]. 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,+21[5]/46,XY[17] 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,+21[10]/46,XY[30]. 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. CONCLUSION: 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.
Subject(s)
Down Syndrome , Fatty Liver , Female , Pregnancy , Male , Humans , Adult , Amniocentesis , Down Syndrome/diagnosis , Down Syndrome/genetics , Mosaicism , In Situ Hybridization, Fluorescence , Comparative Genomic Hybridization , Trisomy , Fatty Liver/diagnosis , Fatty Liver/genetics , Stillbirth , Cell LineABSTRACT
OBJECTIVE: 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. CASE REPORT: 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,X[4]/46,XX[20]. 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,X[17]/47,XXX[8]/46,XX[121]. She was referred for genetic counseling, and the third amniocentesis performed at 30 weeks of gestation revealed the result of 45,X[3]/47,XXX[2]/46,XX[16]. 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,XXX[7]/45,X[1]/46,XX[32], 47,XXX[13]/46,XX[27] and 47,XXX[2]/46,XX[38], 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. CONCLUSION: 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.
Subject(s)
Amniocentesis , Turner Syndrome , Pregnancy , Infant, Newborn , Female , Humans , Adult , Comparative Genomic Hybridization , In Situ Hybridization, Fluorescence , Trisomy , Karyotyping , Mosaicism , Cell Line , DNAABSTRACT
OBJECTIVE: 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. CASE REPORT: 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,X[22]/47,XXX[10]. 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,X[36]/47,XXX[4] (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,X[33]/47,XXX[7], 45,X[30]/47,XXX[10] and 47,XXX[38]/45,X[2], 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,X[38]/47,XXX[2]. When follow-up at age nine months, the neonate was normal in development. FISH analysis on 102 buccal mucosal cells showed 11% (11/102 cells) mosaicism for monosomy X, 12% (12/102 cells) mosaicism for triple X and 77% (79/102 cells) mosaicism for disomy X. Peripheral blood had a karyotype of 45,X[30]/47,XXX[10]. CONCLUSION: 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.
Subject(s)
Amniocentesis , Turner Syndrome , Pregnancy , Infant, Newborn , Female , Humans , Infant , Adult , In Situ Hybridization, Fluorescence , Comparative Genomic Hybridization , Trisomy , Karyotyping , Karyotype , Mosaicism , Cell LineABSTRACT
OBJECTIVE: We present low-level mosaic trisomy 21 at amniocentesis in a pregnancy with a favorable fetal outcome. CASE REPORT: A 34-year-old, primigravid woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 47,XY,+21 [7]/46,XY [33]. At 23 weeks of gestation, repeat amniocentesis revealed a karyotype of 47,XY,+21 [4]/46,XY [22], and cord blood sampling revealed the karyotype of 47,XY,+21 [5]/46,XY [35]. The parental karyotypes were normal. Quantitative fluorescent polymerase chain reaction (QF-PCR) analysis on uncultured amniocytes and parental bloods excluded UPD 21, array comparative genomic hybridization (aCGH) analysis on uncultured amniocytes revealed the result of arr 21q11.2q22.3 × 2.3, consistent with 30% mosaicism for trisomy 21. Interphase fluorescence in situ hybridization (FISH) analysis on uncultured amniocytes revealed 43.8% (35/80 cells) mosaicism for trisomy 21. The woman was advised to continue the pregnancy, and a phenotypically normal 3,340-g male baby was delivered at 39 weeks of gestation. The cord blood had a karyotypes of 46,XY (40/40 cells). QF-PCR on placenta showed mosaic trisomy 21. When follow-up at age three months, the neonate was normal in phenotype and development. FISH analysis on buccal mucosal cells showed 9% (10/101 cells) mosaicism for trisomy 21, compared with 0% (0/100 cells) in the normal control. CONCLUSION: Low-level mosaic trisomy 21 at amniocentesis can be associated with cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes, perinatal progressive decrease of the aneuploid cell line and a favorable fetal outcome.
Subject(s)
Amniocentesis , Down Syndrome , Pregnancy , Infant, Newborn , Female , Male , Humans , Infant , Adult , Down Syndrome/diagnosis , Down Syndrome/genetics , Mosaicism , Comparative Genomic Hybridization , In Situ Hybridization, Fluorescence , Trisomy/diagnosis , Trisomy/genetics , Karyotyping , Karyotype , Cytogenetic AnalysisABSTRACT
OBJECTIVE: We present genetic counseling of a prenatally detected familial 18.79-kb Xp21.1 microduplication encompassing exon 13 of DMD in a pregnancy with no apparent phenotypic abnormalities in the male carriers in the family. CASE REPORT: A 35-year-old, gravida 2, para 0, woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 46,XY. Simultaneous aCGH analysis on the DNA extracted from uncultured amniocytes revealed an 18.79-kb Xp21.1 microduplication, or arr Xp21.1 (32,608,400-32,627,193) × 2.0 [GRCh37 (hg19)] encompassing only exon 13 of the gene of DMD (31,137,345-33,357,706) [GRCh37 (hg19)]. Multiplex ligation-dependent probe amplification (MLPA) analysis of the family showed that the mother and her 32-year-old brother carried the same duplication but without apparent phenotypic abnormalities and no features of DMD. Prenatal ultrasound was normal. She was referred for genetic counseling at 24 weeks of gestation, and continuing pregnancy was advised. At 38 weeks of gestation, a 3530-g phenotypically normal male baby was delivered. aCGH analysis of the umbilical cord confirmed the result of arr Xp21.1 (32,608,400-32,627,193) × 2.0 [GRCh37 (hg19)] encompassing only exon 13 of the gene of DMD (31,137,345-33,357,706) [GRCh37 (hg19)]. CONCLUSION: Xp21.1 microduplication encompassing exon 13 of the DMD gene can be a benign genetic variant.
Subject(s)
Amniocentesis , Genetic Counseling , Humans , Infant , Female , Pregnancy , Male , Adult , Exons/genetics , Gravidity , KaryotypeABSTRACT
OBJECTIVE: We present high-level mosaicism for 45,X in 45,X/46,X,+mar at amniocentesis in a pregnancy associated with positive non-invasive prenatal testing (NIPT) for Turner syndrome, normal male external genitalia and positive SRY in the fetus, a favorable fetal outcome, postnatal decrease of the 45,X cell line and cytogenetic discrepancy in various tissues. CASE REPORT: A 35-year-old, gravida 2, para 1, woman underwent amniocentesis at 16 weeks of gestation because of positive NIPT for Turner syndrome (Z score = -11.72 for X chromosome) at 10 weeks of gestation. Amniocentesis revealed a karyotype of 45,X[13]/46,X,+mar[8]. Simultaneous molecular analysis on the DNA extracted from uncultured amniocytes revealed the results of arr (X) × 1, (Yp) × 0-1 (0.63), (Yq) × 0, (1-22) × 2 in array comparative genomic hybridization (aCGH) and rsa(X) × 1, Yp11.31 × 0-1, Yq11.21 × 0, (13, 18, 21) × 2 in multiplex ligation-dependent probe amplification (MLPA). The parental karyotypes were normal. Prenatal ultrasound revealed normal male external genitalia. She was referred for genetic counseling, and continuing pregnancy was advised. A 2875-g male baby was delivered at 38 weeks of gestation with normal male external genitalia. The karyotypes of cord blood, umbilical cord and placenta were 46,X,+mar[27]/45,X[13], 46,X,+mar[24]/45,X[16] and 45,X[22]/46,X,+mar[18], respectively. SRY testing on cord blood revealed a positive result. When follow-up at age two months, the neonate was normal in development. The karyotype of peripheral blood was 46,X,+mar[25]/45,X[13]/46,X,idic r(Y) [2]. Interphase fluorescence in situ hybridization (FISH) analysis on 103 buccal mucosal cells using Yp11.2-specific probe RP11-119E4 and Xp22.31-specific probe RP11-143E20 showed that 90 cells (90/103 = 87%) had double Yp signals, 3 cells (3/103 = 3%) had single Yp signal and 10 cells (10/103 = 10%) had no Yp signal. CONCLUSION: High-level mosaicism for 45,X in 45,X/46,X,+mar at amniocentesis with positive Yp and SRY can be associated with a favorable fetal outcome, postnatal decrease of the 45,X cell line and cytogenetic discrepancy in various tissues.
Subject(s)
Mosaicism , Turner Syndrome , Male , Female , Pregnancy , Humans , Turner Syndrome/diagnosis , Turner Syndrome/genetics , Comparative Genomic Hybridization , Amniocentesis , In Situ Hybridization, Fluorescence , Fetus , Karyotyping , Cell Line , GenitaliaABSTRACT
OBJECTIVE: 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. CASE REPORT: 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 [0.36]dn 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 [0.34]dn 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. CONCLUSION: 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.
Subject(s)
Breast Neoplasms , Organic Anion Transporters , Male , Female , Pregnancy , Humans , Mosaicism , Amniocentesis , Comparative Genomic Hybridization , In Situ Hybridization, Fluorescence , Genetic Predisposition to Disease , RecQ Helicases , Aneuploidy , Cell Line , Liver-Specific Organic Anion Transporter 1ABSTRACT
OBJECTIVE: We present low-level mosaic trisomy 2 at amniocentesis in a pregnancy associated with positive non-invasive prenatal testing (NIPT) and chorionic villus sampling (CVS) results for trisomy 2, maternal uniparental disomy (UPD) 2, perinatal progressive decrease of the aneuploid cell line, cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes, intrauterine growth restriction (IUGR) and a favorable fetal outcome. CASE REPORT: A 35-year-old, primigravid woman underwent amniocentesis at 16 weeks of gestation because both NIPT at 9 weeks of gestation and CVS at 11 weeks of gestation revealed trisomy 2. This pregnancy was conceived by in vitro fertilization (IVF) and embryo transfer (ET). Amniocentesis revealed a karyotype of 47,XY,+2[11]/46,XY[19]. Prenatal ultrasound findings were normal. She was referred to the hospital for genetic counseling at 20 weeks of gestation, and repeat amniocentesis performed at 24 weeks of gestation revealed a karyotype of 46,XY (22/22 colonies). The parental karyotypes were normal. Quantitative fluorescent polymerase chain reaction (QF-PCR) analysis on the DNA extracted from uncultured amniocytes and parental bloods revealed maternal uniparental heterodisomy of chromosome 2. Simultaneous molecular cytogenetic analysis on uncultured amniocytes showed the results of arr 2p25.3q37.3 × 2.4 with a log2 ratio = 0.26, consistent with 40% mosaicism for trisomy 2 by array comparative genomic hybridization (aCGH), and 28% (28/100 cells) mosaicism for trisomy 2 by interphase fluorescence in situ hybridization (FISH). Despite IUGR on fetal ultrasound, the woman was advised to continue the pregnancy, and a 2252-g phenotypically normal male baby was delivered at 38 weeks of gestation. The karyotypes of cord blood, umbilical cord and placenta were 46,XY (40/40 colonies), 46,XY (40/40 colonies) and 47,XY,+2[9]/46,XY[31], respectively. QF-PCR analysis on cord blood, umbilical cord and placenta confirmed uniparental heterodisomy of chromosome 2 in the cord blood and umbilical cord, and maternal origin of trisomy 2 in the placenta. FISH analysis on buccal mucosal cells at age 1.5 months revealed 8.7% (9/104 cells) mosaicism for trisomy 2. When follow-up at age four months, the neonate manifested a normal phenotype except intermittent hypoventilation. Molecular analysis of the PHOX2B gene revealed a normal result. When follow-up at age one year, he manifested normal development. CONCLUSION: Mosaic trisomy 2 at prenatal diagnosis should alert the possibility of UPD 2 and include a UPD 2 testing. Low-level mosaic trisomy 2 at amniocentesis can be associated with perinatal progressive decrease of the aneuploid cell line and a favorable fetal outcome.
Subject(s)
Amniocentesis , Chorionic Villi Sampling , Pregnancy , Female , Male , Humans , Amniocentesis/methods , Uniparental Disomy/genetics , Trisomy/diagnosis , Trisomy/genetics , Fetal Growth Retardation/diagnosis , Fetal Growth Retardation/genetics , Comparative Genomic Hybridization , In Situ Hybridization, Fluorescence , Chromosomes, Human, Pair 2/genetics , Cytogenetic Analysis/methods , Chromosome Aberrations , MosaicismABSTRACT
OBJECTIVE: We present low-level mosaic trisomy 13 at amniocentesis in a pregnancy associated with a positive non-invasive prenatal testing (NIPT) result suspicious of trisomy 13, a chorionic villus sampling (CVS) result of mosaic trisomy 13, cytogenetic discrepancy in various tissues and a favorable fetal outcome. CASE REPORT: A 29-year-old, gravida 2, para 1, woman underwent amniocentesis at 20 weeks of gestation because of a positive NIPT result (Z-score = 20.9, positive ≥3) suspicious of trisomy 13 at 11 weeks of gestation and a CVS result of mosaic trisomy 13 at 14 weeks of gestation. At 14 weeks of gestation, CVS revealed the multiplex ligation-dependent probe amplification (MLPA) result of rea X,Y (P095) × 1, 13 (P095) × 3, 18,21 (P095) × 2/X,Y (P095) × 1, 13,18,21 (P095) × 2 and a karyotype of 48,XY,+13,+mar [9]/47,XY,+mar[16]. She was referred to the hospital for genetic counseling at 15 weeks of gestation, and cytogenetic analysis of parental blood revealed 47,XY,+mar in the father and 46, XX in the mother. Fluorescence in situ hybridization (FISH) analysis on the paternal blood showed that the extra dicentric marker was derived from chromosome 15 without the locus SNRPN (15q11.2), and the result was 47,XY,+mar.ish dic(15) (D15Z1++, SNRPN-, PML-)[20]. Amniocentesis at 20 weeks of gestation revealed a karyotype of 47,XY,+mar pat (20/20). Simultaneous interphase FISH analysis on uncultured amniocytes revealed 32% (32/100 cells) mosaicism for trisomy 13. Quantitative fluorescence polymerase chain reaction (QF-PCR) analysis using the DNA extracted from the parental bloods and uncultured amniocytes excluded uniparental disomy (UPD) 13. Prenatal ultrasound findings were normal. The woman was advised to continue the pregnancy, and a phenotypically normal 2708-g male baby was delivered at 38 weeks of gestation, The cord blood, umbilical cord and placenta had the karyotypes of 47,XY,+mar pat and did not have UPD 13. When follow-up at age two months, the neonate was phenotypically normal. FISH analysis on buccal mucosal cells detected 5.3% (5/95 cells) mosaicism for trisomy 13, compared with 0% in the normal control. CONCLUSION: Low-level mosaic trisomy 13 at amniocentesis can be associated with a positive NIPT result suspicious of trisomy 13, a CVS result of mosaic trisomy 13, cytogenetic discrepancy in various tissues and a favorable fetal outcome.