Low-level mosaic trisomy 9 at amniocentesis associated with a positive non-invasive prenatal testing for trisomy 9, maternal uniparental disomy 9, intrauterine growth restriction and a favorable fetal outcome in a pregnancy.

OBJECTIVE: We present low-level mosaic trisomy 9 at amniocentesis associated with a positive non-invasive prenatal testing (NIPT) for trisomy 9, maternal uniparental disomy (UPD) 9, intrauterine growth restriction (IUGR) and a favorable fetal outcome in a pregnancy. CASE REPORT: A 41-year-old, gravida 3, para 0, woman underwent amniocentesis at 18 weeks of gestation because of NIPT at 10 weeks of gestation suspicious of trisomy 9 in the fetus. This pregnancy was conceived by in vitro fertilization (IVF). Amniocentesis revealed a karyotype of 47,XY,+9 [2]/46,XY[23]. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed arr (1-22) × 2, (X,Y) × 1 and detected no genomic imbalance. Polymorphic DNA marker analysis showed maternal uniparental heterodisomy 9 in the amniocytes. Prenatal ultrasound was normal. The woman was referred for genetic counseling at 22 weeks of gestation. The soluble fms-like tyrosine kinase (sFlt)/placental growth factor (PlGF) = 13.1 (normal < 38). There was no gestational hypertension. Continuing the pregnancy was advised. No repeat amniocentesis was performed because of persistent irregular contractions. IUGR was noted. A 2156-g phenotypically normal baby was delivered at 37 weeks of gestation. The cord blood and umbilical cord had a karyotype of 46,XY (40/40 cells). The placenta had a karyotype of 47,XY,+9 (40/40 cells). The parental karyotypes were normal. Quantitative fluorescence polymerase chain reaction (QF-PCR) on the DNA extracted from parental bloods, cord blood, umbilical cord and placenta revealed maternal uniparental heterodisomy 9 in cord blood and umbilical cord, and trisomy 9 of maternal origin in placenta. When follow-up at age three months, the neonate was normal in development and phenotype. The buccal mucosal cells had 3% (3/101 cells) mosaicism for trisomy 9 by interphase fluorescent in situ hybridization (FISH) analysis. CONCLUSION: Mosaic trisomy 9 at prenatal diagnosis should alert the possibility of UPD 9 and include a UPD 9 testing. Low-level mosaic trisomy 9 at amniocentesis can be associated with UPD 9 and a favorable fetal outcome.

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.

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

Prenatal diagnosis and molecular genetic analysis of recurrent trisomy 18 of maternal origin in two consecutive pregnancies.

OBJECTIVE: We present prenatal diagnosis and molecular genetic analysis of recurrent trisomy 18 of maternal origin in two consecutive pregnancies. CASE REPORT: A 37-year-old, gravida 3, para 1, woman was referred for genetic counseling because of cystic hygroma on ultrasound at 12 weeks of gestation, a previous pregnancy with a fetus with trisomy 18, and an abnormal first-trimester non-invasive prenatal testing (NIPT) result of Z score of 9.74 (normal: -3.0-3.0) in chromosome 18 suggesting trisomy 18 during this pregnancy. The fetus died at 14 weeks of gestation, and a malformed fetus was terminated at 15 weeks of gestation. Cytogenetic analysis of the placenta revealed a karyotype of 47,XY,+18. Quantitative fluorescent polymerase chain reaction (QF-PCR) assays on the DNA extracted from parental bloods and umbilical cord determined a maternal origin of trisomy 18. One year previously, the woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age of 36 years. Amniocentesis revealed a karyotype of 47,XX,+18. Prenatal ultrasound was unremarkable. The mother had a karyotype of 46,XX, and the father had a karyotype of 46,XY. QF-PCR assays on the DNA extracted from parental bloods and cultured amniocytes determined a maternal origin of trisomy 18. The pregnancy was subsequently terminated. CONCLUSION: NIPT is useful for rapid prenatal diagnosis of recurrent trisomy 18 under such a circumstance.

Low-level mosaic trisomy 20 without uniparental disomy 20 at amniocentesis in a pregnancy associated with a favorable outcome, cytogenetic discrepancy between uncultured amniocytes and cultured amniocytes and perinatal progressive decrease of the aneuploid cell line.

OBJECTIVE: We present low-level mosaic trisomy 20 without uniparental disomy (UPD) 20 at amniocentesis in a pregnancy associated with a favorable outcome, cytogenetic discrepancy between uncultured amniocytes and cultured amniocytes and perinatal progressive decrease of the aneuploid cell line. CASE REPORT: A 36-year-old, gravida 2, para 1, woman underwent amniocentesis at 16 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 47,XY,+20[3]/46,XY[17]. Array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed the result of arr (1-22) × 2, X × 1, Y × 1 with no genomic imbalance. Prenatal ultrasound was unremarkable. She was referred for genetic counseling at 23 weeks of gestation, and repeat amniocentesis was performed. Cytogenetic analysis of the cultured amniocytes revealed a karyotype of 47,XY,+20[1]/46,XY[27]. Simultaneous aCGH analysis on the DNA extracted from uncultured amniocytes by SurePrint G3 Unrestricted CGH ISCA v2, 8 × 60 K (Agilent Technologies, CA, USA) revealed the result of arr (1-22) × 2, X × 1, Y × 1. Quantitative fluorescent polymerase chain reaction (QF-PCR) assays on the DNAs extracted from uncultured amniocytes and parental bloods excluded UPD 20. The woman was advised to continue the pregnancy, and a healthy 3750-g phenotypically normal male baby was delivered at 38 weeks of gestation. The cord blood had a karyotype of 46,XY (40/40 cells). CONCLUSION: Low-level mosaic trisomy 20 without UPD 20 at amniocentesis can be associated with a favorable outcome. Progressive decrease of the aneuploid cell line can occur in mosaic trisomy 20 at amniocentesis. Low-level mosaic trisomy 20 at amniocentesis can be a transient and benign condition.

Molecular cytogenetic characterization of del(X)(p22.33)mat and de novo dup(4)(q34.3q35.2) in a male fetus with multiple anomalies of facial dysmorphism, ventriculomegaly, congenital heart defects, short long bones and clinodactyly.

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

Low-level mosaic double trisomy involving trisomy 6 and trisomy 20 (48,XY,+6,+20) at amniocentesis without uniparental disomy (UPD) 6 and UPD 20 in a pregnancy associated with a favorable outcome.

OBJECTIVE: We present low-level mosaic double trisomy involving trisomy 6 and trisomy 20 (48,XY,+6,+20) at amniocentesis without uniparental disomy (UPD) 6 and UPD 20 in a pregnancy associated with a favorable outcome. CASE REPORT: A 38-year-old woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 48,XY,+6,+20[2]/46,XY[15]. Repeat amniocentesis at 20 weeks of gestation revealed a karyotype of 48,XY,+6,+20[6]/46,XY[43], and simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed the result of arr (X,Y) × 1, (1-22) × 2 with no genomic imbalance. At 22 weeks of gestation, the woman underwent cordocentesis which revealed karyotype of 46,XY (60/60 cells). At 26 weeks of gestation, the woman underwent the third amniocentesis which revealed a karyotype of 48,XY,+6,+20[5]/46,XY[30], and simultaneous aCGH analysis on the DNA extracted from uncultured amniocytes revealed the result of arr (1-22) × 2, X × 1, Y × 1 without genomic imbalance. The parental karyotypes and prenatal ultrasound were normal. Polymorphic marker analysis using the DNAs extracted from uncultured amniocytes and parental bloods excluded UPD 6 and UPD 20. Interphase fluorescence in situ hybridization (FISH) analysis on 100 uncultured amniocytes detected double trisomy 6 and trisomy 20 in 10 cells, consistent with 10% (10/100 cells) mosaicism for double trisomy 6 and trisomy 20. The woman was encouraged to continue the pregnancy, and a phenotypically normal 3328-g male baby was delivered at 38 weeks of gestation. The cord blood, umbilical cord and the placenta had a karyotype of 46,XY (40/40 cells). CONCLUSION: Low-level mosaic double trisomy involving trisomy 6 and trisomy 20 at amniocentesis without UPD 6 and UPD 20 can be associated with a favorable fetal outcome.

[Clinical analysis of monochorionic-diamniotic twins with genetic discordance].

OBJECTIVE: To explore the genetic etiology of 5 cases of monochorionic-diamniotic (MCDA) with genetic discordance. METHODS: 148 cases of MCDA twins who were diagnosed by amniocentesis at the Maternal and Child Health Care Hospital of Guangxi Zhuang Autonomous Region from January 2016 to June 2020 were selected as the study subjects. Relevant clinical data of the pregnant women were collected, and amniotic fluid samples of the twins were collected separately. Chromosomal karyotyping analysis and single nucleotide polymorphism array (SNP array) assay were carried out. RESULTS: The results of chromosomal karyotyping analysis showed that 5 of the MCDA twins had inconsistent chromosome karyotypes, with an incidence of 3.4% (5/148). SNP array assay showed that 3 fetuses were mosaics. CONCLUSION: Genetic discordance occurs among MCDA twins, and prenatal counseling for such cases should be given by doctors with experience in medical genetics and fetal medicine, and personalized clinical management should be recommended.

Mosaic 46,XY,dup(14) (q12q22.3)/46, XY at amniocentesis in a pregnancy associated with a favorable fetal outcome and cytogenetic discrepancy in various tissues.

OBJECTIVE: We present mosaic 46,XY,dup (14) (q12q22.3)/46, XY at amniocentesis in a pregnancy associated with a favorable fetal outcome and cytogenetic discrepancy in various tissues. CASE REPORT: A 41-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. Cytogenetic analysis on cultured amniocytes revealed a karyotype of 46,XY, dup (14) (q12q22.3)[7]/46,XY [13], and simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed arr 14q12q22.3 × 2-3 with 25% mosaicism for partial 14q duplication. She was referred for genetic counseling. Prenatal ultrasound and parental karyotypes were normal. Repeat amniocentesis at 22 weeks of gestation revealed a karyotype of 46,XY,dup (14) (q12q22.3)[6]/46,XY [14], and in uncultured amniocytes, quantitative fluorescence polymerase chain reaction (QF-PCR) analysis excluded uniparental disomy (UPD) 14, aCGH revealed arr 14q12q22.3 × 2.3 with 30% mosaicism for dup (14) (q12q22.3), and interphase fluorescence in situ hybridization (FISH) showed 19.4% (24/124 cells) mosaicism for partial 14q duplication. She was encouraged to continue the pregnancy, and a 2450-g phenotypically normal male baby was delivered at 40 weeks of gestation. The karyotypes of cord blood, umbilical cord and placenta were 46,XY,dup (14) (q12q22.3)[14]/46,XY [26], 46,XY,dup (14) (q12q22.3)[7]/46,XY [33] and 46,XY,dup (14) (q12q22.3)[3]/46,XY [37], respectively. When follow-up at age four months, the neonate was phenotypically normal. The karyotype of peripheral blood was 46,XY,dup (14) (q12q22.3)[27]/46,XY [13], and interphase FISH analysis on 105 buccal mucosal cells detected partial 14q duplication signals in 5 cells (4.8% mosaicism). When follow-up at age nine months, the neonate was phenotypically normal. The karyotype of peripheral blood was 46,XY,dup (14) (q12q22.3)[25]/46,XY [15]. CONCLUSION: Mosaic dup (14) (q12q22.3) with a normal cell line at amniocentesis may be a benign condition, and can be associated with a favorable fetal outcome and cytogenetic discrepancy in various tissues.

Low-level mosaic trisomy 15 at amniocentesis without uniparental disomy 15 in a pregnancy associated with cytogenetic discrepancy between uncultured amniocytes and cultured amniocytes, a favorable fetal outcome and perinatal decrease of the aneuploid cell line.

OBJECTIVE: We present low-level mosaic trisomy 15 without uniparental disomy (UPD) 15 in a pregnancy associated with cytogenetic discrepancy between uncultured amniocytes and cultured amniocytes, a favorable fetal outcome and perinatal decrease of the aneuploid cell line. CASE REPORT: A 40-year-old, gravida 2, para 0, woman underwent amniocentesis at 16 weeks of gestation because advanced maternal age. This pregnancy was conceived by in vitro fertilization and embryo transfer. Amniocentesis revealed a karyotype of 47,XX,+15 [7]/46,XX [43]. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed arr (15) × 2-3 (X) × 2 with 14% mosaicism for trisomy 15, and ME028 multiplex ligation-dependent probe amplification (MLPA) methylation test excluded UPD 15. Prenatal ultrasound and parental karyotypes were normal. She was referred for genetic counseling, and repeat amniocentesis performed at 28 weeks of gestation revealed 46, XX (20/20 colonies) in cultured amniocytes, and in uncultured amniocytes, interphase fluorescence in situ hybridization (FISH) showed 13.7% (16/117 cells) mosaicism for trisomy 15, aCGH analysis revealed arr [GRCh(hg19)] 15q11.22q26.3 (22, 765, 628-102,256,748) × 2.4 with a log2 ratio = 0.26, consistent with 40% mosaicism for trisomy 15, and quantitative fluorescent polymerase chain reaction (QF-PCR) assays excluded UPD 15. The woman was encouraged to continue the pregnancy. At 37 weeks of gestation, a 2400-g phenotypically normal female baby was delivered without any abnormality. The cord blood had 46, XX (40/40 cells). QF-PCR assays determined maternal origin of trisomy 15 in the placenta. When follow-up at age 5 months, the neonate was normal in physical and psychomotor development. FISH analysis on 102 buccal mucosal cells detected 2 cells (2%, 2/102 cells) with trisomy 15 signals, compared with 1% in normal control. CONCLUSIONS: Low-level mosaic trisomy 15 at amniocentesis without UPD 15 can be a transient and benign condition, and can be associated with a favorable fetal outcome and perinatal decrease of the aneuploid cell line.

Low-level mosaic trisomy 13 at amniocentesis in a pregnancy associated with a favorable fetal outcome and cytogenetic discrepancy in various tissues.

OBJECTIVE: We present low-level mosaic trisomy 13 at amniocentesis in a pregnancy associated with associated with a favorable fetal outcome and cytogenetic discrepancy in various tissues. CASE REPORT: A 38-year-old, gravida 3, para 0, woman underwent amniocentesis at 19 weeks of gestation because of advanced maternal age. This pregnancy was conceived by in vitro fertilization and embryo transfer. Amniocentesis revealed a karyotype of 47,XX,+13[2]/ 46,XX[20] in co-twin A and a karyotype of 46,XY in co-twin B. In co-twin A, among 22 colonies of cultured amniocytes, two colonies had a karyotype of 47,XX,+13, whereas the rest 20 colonies had the karyotype of 46,XX. Array comparative genomic hybridization (aCGH) analysis on the DNA extracted from cultured amniocytes revealed arr (1-22,X) × 2, Y × 0 and detected no genomic imbalance. Prenatal ultrasound and parental karyotypes were normal. Quantitative fluorescence polymerase chain reaction (QF-PCR) analysis on the DNA extracted from the parental bloods and cultured amniocytes excluded uniparental disomy (UPD) 13. The woman was encouraged to continue the pregnancy. At 37 weeks of gestation, a normal 2410-g female co-twin A and a normal 2360-g male co-twin B were delivered without any phenotypic abnormality. The karyotypes of cord blood, umbilical cord and placenta of co-twin A were 46,XX (40/40 cells), 47,XX,+13 [1]/46,XX[39] and 47,XX,+13[36]/46,XX [4], respectively. QF-PCR analysis on cord blood of co-twin A excluded UPD 13. When follow-up at age 1½ years, the neonate of co-twin A was normal in physical and psychomotor development. CONCLUSION: Low-level true mosaic trisomy 13 at amniocentesis can be associated with a favorable fetal outcome and cytogenetic discrepancy in various tissues.

[Genetic analysis of a fetus with mosaic trisomy 12 and severe heart defects and a literature review].

OBJECTIVE: To explore the genetic basis for a fetus with severe heart defect and mosaic trisomy 12, and the correlation between chromosomal abnormalities and clinical manifestations and pregnancy outcome. METHODS: A 33-year-old pregnant woman who presented at Lianyungang Maternal and Child Health Care Hospital on May 17, 2021 due to abnormal fetal heart development revealed by ultrasonography was selected as the study subject. Clinical data of the fetus were collected. Amniotic fluid sample of the pregnant women was collected and subjected to G-banded chromosomal karyotyping and chromosomal microarray analysis (CMA). The CNKI, WanFang and PubMed databases were searched with key words, with the retrieval period set as from June 1, 1992 to June 1, 2022. RESULTS: For the 33-year-old pregnant woman, ultrasonography at 22+6 gestational weeks had revealed abnormal fetal heart development and ectopic pulmonary vein drainage. G-banded karyotyping showed that the fetus has a karyotype of mos 47,XX,+12[1]/46,XX[73], with the mosaicism rate being 1.35%. CMA results suggested that about 18% of fetal chromosome 12 was trisomic. A newborn was delivered at 39 weeks of gestation. Follow-up confirmed severe congenital heart disease, small head circumference, low-set ears and auricular deformity. The infant had died 3 months later. The database search has retrieved 9 reports. Literature review suggested that the liveborn infants with mosaic trisomy 12 had diverse clinical manifestations depending on the affected organs, which had included congenital heart disease and/or other organs and facial dysmorphisms, resulting in adverse pregnancy outcomes. CONCLUSION: Trisomy 12 mosaicism is an important factor for severe heart defects. The results of ultrasound examination have important value for evaluating the prognosis of the affected fetuses.

Mosaic 45,X/46, XX at amniocentesis with high-level mosaicism for 45,X in a pregnancy with a favorable fetal outcome and postnatal decrease of the 45,X cell line.

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

Low-level mosaic trisomy 17 at amniocentesis in a pregnancy associated with a favorable fetal outcome and cytogenetic discrepancy between cultured and uncultured amniocytes.

OBJECTIVE: We present low-level mosaic trisomy 17 at amniocentesis in a pregnancy associated with a favorable fetal outcome and cytogenetic discrepancy between cultured and uncultured amniocytes. CASE REPORT: A 32-year-old, primigravid woman underwent amniocentesis at 18 weeks of gestation because of an increased nuchal translucency thickness of 3 mm in the first trimester sonographic screening. Amniocentesis revealed a karyotype of 47,XX,+17 [2]/46,XX [20]. Among 22 colonies of cultured amniocytes, two colonies had a karyotype of 47,XX,+17, whereas the rest 20 colonies had a karyotype of 46,XX. Simultaneous array comparative genomic hybridization (aCGH) on the DNA extracted from uncultured amniocytes revealed arr (1-22,X) × 2 with no genomic imbalance. Prenatal ultrasound and parental karyotypes were normal. Quantitative fluorescence polymerase chain reaction (QF-PCR) analysis on the DNA extracted from the parental bloods and cultured amniocytes excluded uniparental disomy (UPD) 17. The woman was encouraged to continue the pregnancy. A normal 3178-g female baby was delivered at 38 weeks of gestation without any phenotypic abnormalities. The karyotypes of cord blood, umbilical cord and placenta were all 46, XX (40/40 cells). When follow-up at age six months, the neonate was normal in physical and psychosomatic development. CONCLUSION: Low-level mosaic trisomy 17 at amniocentesis can be a transient and benign condition, and can be associated with a favorable fetal outcome and cytogenetic discrepancy between cultured and uncultured amniocytes.

Second-trimester amniotic fluid proteins changes in subsequent spontaneous preterm birth.

INTRODUCTION: The global sequence of the pathogenesis of preterm labor remains unclear. This study aimed to compare amniotic fluid concentrations of extracellular matrix-related proteins (procollagen, osteopontin and IL-33), and of cytokines (IL-19, IL-6, IL-20, TNFα, TGFß, and IL-1ß) in asymptomatic women with and without subsequent spontaneous preterm delivery. MATERIAL AND METHODS: We used amniotic fluid samples of singleton pregnancy, collected by amniocentesis between 16 and 20 weeks' gestation, without stigmata of infection (i.e., all amniotic fluid samples were tested with broad-range 16 S rDNA PCR to distinguish samples with evidence of past bacterial infection from sterile ones), during a randomized, double-blind, placebo-controlled trial to perform a nested case-control laboratory study. Cases were women with a spontaneous delivery before 37 weeks of gestation (preterm group). Controls were women who gave birth at or after 39 weeks (full term group). Amniotic fluid concentrations of the extracellular matrix-related proteins and cytokines measured by immunoassays were compared for two study groups. CLINICALTRIALS: gov: NCT00718705. RESULTS: Between July 2008 and July 2011, in 12 maternal-fetal medicine centers in France, 166 women with available PCR-negative amniotic fluid samples were retained for the analysis. Concentrations of procollagen, osteopontin, IL-19, IL-6, IL-20, IL-33, TNFα, TGFß, and IL-1ß were compared between the 37 who gave birth preterm and the 129 women with full-term delivery. Amniotic fluid levels of procollagen, osteopontin, IL-19, IL-33, and TNFα were significantly higher in the preterm than the full-term group. IL-6, IL-20, TGFß, and IL-1ß levels did not differ between the groups. CONCLUSIONS: In amniotic fluid 16 S rDNA PCR negative samples obtained during second-trimester amniocentesis, extracellular matrix-related protein concentrations (procollagen, osteopontin and IL-33), together with IL-19 and TNFα, were observed higher at this time in cases of later spontaneous preterm birth.

A Case Report of a Feto-Placental Mosaicism Involving a Segmental Aneuploidy: A Challenge for Genome Wide Screening by Non-Invasive Prenatal Testing of Cell-Free DNA in Maternal Plasma.

Non-invasive prenatal testing (NIPT) using cell-free DNA can detect fetal chromosomal anomalies with high clinical sensitivity and specificity. In approximately 0.1% of clinical cases, the NIPT result and a subsequent diagnostic karyotype are discordant. Here we report a case of a 32-year-old pregnant patient with a 44.1 Mb duplication on the short arm of chromosome 4 detected by NIPT at 12 weeks' gestation. Amniocentesis was carried out at 18 weeks' gestation, followed by conventional and molecular cytogenetic analysis on cells from the amniotic fluid. SNP array analysis found a de novo deletion of 1.2 Mb at chromosome 4, and this deletion was found to be near the critical region of the Wolf-Hirschhorn syndrome. A normal 46,XY karyotype was identified by G-banding analysis. The patient underwent an elective termination and molecular investigations on tissues from the fetus, and the placenta confirmed the presence of type VI true fetal mosaicism. It is important that a patient receives counselling following a high-risk call on NIPT, with appropriate diagnostic analysis advised before any decisions regarding the pregnancy are taken. This case highlights the importance of genetic counselling following a high-risk call on NIPT, especially in light of the increasing capabilities of NIPT detection of sub-chromosomal deletions and duplications.

Phenotypic Spectrum of Trisomy 18 Mosaicism: a New Patient and Literature Review.

BACKGROUND: Trisomy 18 syndrome, also called Edwards syndrome, is the second most common autosomal trisomy after trisomy 21 that is caused by the presence of an extra copy of chromosome 18. Approximately 50% of infants with trisomy 18 cannot survive for more than 1 week and about 5 - 10% of children die within 1 year after birth. The aim of this study is to describe a 4-year-old female patient of mosaic trisomy 18 with normal prenatal ultrasound findings and maternal serum markers and to investigate the relationship between the percentage of trisomic cells and the major clinical phenotypes combined with other nine patients through a review of the literature. METHODS: The patient's peripheral blood was examined by cytogenetic G-banding technique. RESULTS: The cytogenetics results reported following the ISCN 2020 guideline as mos 47,XX,+18[87]/46,XX[13]. CONCLUSIONS: There is little correlation between various phenotypes of mosaic trisomy 18 and the percentage of trisomy cells in the patient's peripheral leukocytes. Although most of fetuses with mosaic trisomy 18 have abnormal ultrasound findings, it is necessary to highlight the possibility of normal findings during the pregnancy.

Contribution of amniocentesis in fetuses small for gestational age without other sonographic signs.

OBJECTIVE: Our study evaluated the contribution of amniocentesis in the diagnostic approach of small-for-gestational-age fetuses (SGA) without morphological abnormality identified on ultrasound by studying FISH (fluorescence in situ hybridization) for chromosomes 13, 18 and 21, CMV PCR (cytomegalovirus polymerase chain reaction), karyotype and CGH (genomic hybridization array) METHODS: Our single-center retrospective cohort study included pregnant women referred for prenatal diagnosis for a SGA fetus in whom amniocentesis was performed between 2016 and 2019. A SGA fetus was defined as a fetus with an estimated fetal weight (EFW) below the 10th percentile according to referral growth curves in use. We evaluated the number of amniocenteses with an abnormal result and identified factors that may be associated with this outcome. RESULTS: Among the 79 amniocenteses performed, there were 5 (6.3%) abnormalities: karyotype (1.3%) and CGH (5.1%). No complications were described. We did not find any statistically significant factors associated with abnormal amniocentesis findings even if some elements seemed reassuring such as late discovery (p = 0.31), moderate SGA (p = 0.18), normal head, abdomen and femur measurements (p = 0.57), but without statistically significant difference. CONCLUSION: Our study found 6.3% pathological analysis of amniocenteses, of which several would have been missed by conventional karyotyping. Patients must be informed about the risk of detecting abnormalities of low severity, with low penetrance or with unknown fetal consequences that could be source of anxiety.

Fetal hemivertebra: a rare form of 18q deletion prenatal presentation.

The 18q deletion is a rare condition with several described features. A common phenotype includes short stature, microcephaly, facial defects, small feet, intellectual disability and hypotonia.We present a rare case of a fetus with del18q22.1q23 whose diagnosis was obtained by amniocentesis after a routine ultrasound at 20 weeks, where a hemivertebra was detected.Congenital hemivertebra is infrequent and is rarely associated with chromosomal anomalies. Expectant management can be advocated in isolated hemivertebra. This report shows that a hemivertebra can be an isolated prenatal finding in del18 so it is important to screen for, and exclude, chromosomal anomalies.