Prenatal Diagnosis Of Mosaic Trisomy Research Articles

Prenatal diagnosis of mosaic trisomy 2 and literature review

BackgroundWe presented two cases of mosaic trisomy 2 with high risk of maternal serum screening and non-invasive prenatal testing (NIPT). The invasive amniocentesis was performed and genetic tests including karyotype, single nucleotide polymorphism array(SNP-array), interphase fluorescence in situ hybridization (FISH) were employed to detect the chromosomal abnormality.ResultsCytogentic analysis of the case 1 and 2 showed a mosaic karyotype consisting of two cell lines (mos 47,XY,+2[8]/46,XY[19] and mos 47,XX,+2[7]/46,XX[28], respectively). SNP-array using DNA extracted from uncultured amniotic fluid cells revealed a result of arr[GRCh38](2)x2~3, which indicated that chromosome 2 may be trisomy of mosaicism in both two cases. The results of interphases FISH confirmation test showed that three red signals of the CEP 2 specific probe in 14%(14/100) and 12%(12/100) of the two cases’ cells, respectively, which indicated a mosaicism for trisomy 2 in the uncultured amniocytes. Fetal ultrasound of case 1 suggested that the long bone is smaller than the gestational age, while the case 2 showed that the biparietal diameter (BPD), head circumference (HC) and femur length (FL) were smaller than gestational age along with abnormal cardiac structure.ConclusionsWe presented two cases with mosaic trisomy 2 and performed confirmatory genetic testing using cultured and uncultured amniocytes. When maternal serum screening and NIPT suggesting high risk, genetic counselor should be alert for increasing possibility of chromosomal anomalies if combined with abnormal ultrasound findings.

Prenatal diagnosis of mosaic trisomy 2: a case report

We reported a case of mosaic trisomy 2. The patient was a 29-year-old gravida who underwent amniocentesis at 20 weeks of gestation because of high risk of trisomy-21 in the first trimester screening. The test result revealed a karyotype of 47, XN, +2[10]/46, XX[40]. At 26 gestational weeks, the fetus was found severe fetal growth restriction and oligohydramnios which was considered to be at risk of mosaic trisomy 2. The pregnancy was terminated at 27+ gestational weeks. The fetus had obviously abnormal appearances, including dolichocephaly, low-set ears, and micromandible. Autopsy was not performed due to the parents' refusal. Key words: Trisomy; Chromosomes, human, pair 2; Chimera; Prenatal diagnosis; Amniocentesis; Abnormalities, multiple

A prenatal diagnosis of mosaic trisomy 5 reveals a postnatal complete uniparental disomy of chromosome 5 with multiple congenital anomalies

Mosaic trisomy 5 is a very rare condition in liveborns, with few cases reported in the last four decades. There are some reports of prenatally diagnosed mosaic trisomy 5 resulting in phenotypically normal offspring, suggesting a low level of mosaicism, but there are also reports associated with multiple congenital anomalies, cardiovascular malformations, and intrauterine growth restriction. We report an infant male diagnosed with mosaic trisomy 5 (5/15 cells) via amniocentesis. The patient was subsequently found to have uniparental disomy 5 (UPD5) by postnatal chromosome microarray, but high-resolution chromosome analysis on peripheral blood did not identify trisomy 5. Dysmorphic features included a tall forehead with low anterior hairline, hypertelorism, low-set ears, and a prominent nose and midface. Other anomalies included bilateral bifid thumbs, hypospadias, a perineal fistula, unilateral multicystic kidney, and decreased subcutaneous fat with loose skin. He had complex congenital heart disease consisting of ventricular and atrial septal defects and polyvalvular defects. The patient died at age one after a prolonged admission. We add this case to the literature with the added benefit of data from a postnatal microarray, which was not available in other cases, to broaden the phenotype of mosaic trisomy 5 and UPD5.With the current available technology, we stress the importance of postnatal genetic testing to confirm prenatal cytogenetic findings in order to further define such phenotypes. This will provide the most accurate information and counseling to affected families.

Mosaic trisomy 15 at amniocentesis: Prenatal diagnosis, molecular genetic analysis and literature review

ObjectiveTo present prenatal diagnosis of mosaic trisomy 15 at amniocentesis. Materials and methodsA 37-year-old woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Cytogenetic analysis of cultured amniocytes revealed a karyotype of 47,XY,+15[2]/46,XY[17]. She was referred for repeated amniocentesis at 19 weeks of gestation. Array comparative genomic hybridization (aCGH), interphase fluorescence in situ hybridization (FISH) and quantitative fluorescent polymerase chain reaction assays on uncultured amniocytes, conventional cytogenetic analysis and aCGH on cultured amniocytes, and FISH on uncultured urinary cells after birth were applied. Cordocentesis revealed a karyotype of 46,XY. ResultsAt repeated amniocentesis, cultured amniocytes revealed a karyotypes of 46,XY [22 colonies], FISH on uncultured amniocytes revealed 21.2% (22/104 cells) mosaicism for trisomy 15, aCGH on uncultured amniocytes revealed a genomic gain (log2 ratio = 0.3) in chromosome 15, quantitative fluorescent polymerase chain reaction on uncultured amniocytes excluded uniparental disomy 15 (UPD 15), and aCGH on culture amniocytes revealed no genomic imbalance in chromosome 15. A healthy 3700 g male baby was delivered at 38 weeks of gestation with no phenotypic abnormalities at age 6 months. FISH on uncultured urinary cells at birth and at age 6 months revealed mosaic trisomy 15 levels of 20% (13/65 cells) and 12.2% (6/49 cells), respectively. ConclusionPrenatal diagnosis of mosaic trisomy 15 at amniocentesis should alert doctors about the occurrence of UPD 15 and a clinically significant phenotype. The present case provides evidence for cytogenetic discrepancy between uncultured and cultured amniocytes in mosaic trisomy 15 at amniocentesis. It is possible that the abnormal cell lines of amniocytes with trisomy 15 disappear after long-term cell culture.

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

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

Prenatal diagnosis of mosaic trisomy 12 associated with congenital overgrowth

Prenatal diagnosis of mosaic trisomy 12 associated with congenital overgrowth

Mosaic trisomy 12 at amniocentesis: Prenatal diagnosis and molecular genetic analysis

ObjectiveThis study is aimed at prenatal diagnosis of mosaic trisomy 12 and reviewing the literature. Materials and MethodsA 34-year-old woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Cytogenetic analysis of cultured amniocytes revealed a karyotype of 47,XX,+12[9]/46,XX[14]. She was referred to the hospital for genetic counseling. Repeated amniocentesis was performed at 22 weeks of gestation. Array comparative genomic hybridization (aCGH), interphase fluorescence in situ hybridization (FISH) and quantitative fluorescent polymerase chain reaction (QF-PCR) were applied on uncultured amniocytes, and conventional cytogenetic analysis was applied on cultured amniocytes. ResultsThe aCGH analysis on uncultured amniocytes revealed a small genomic gain in chromosome 12. Interphase FISH analysis on uncultured amniocytes using a 12q11-q12-specific probe of RP11-496H24 (green spectrum) showed three green signals in 17.8% (8/45 cells) of uncultured amniocytes. QF-PCR analysis on uncultured amniocytes using chromosome 12-specific microsatellite markers excluded uniparental disomy 12. Cytogenetic analysis of cultured amniocytes revealed a karyotype of 47,XX,+12[5]/46,XX[25]. The parents decided to continue the pregnancy. A healthy 3270 g female baby was delivered at 39 weeks of gestation, with no phenotypic abnormalities. Cytogenetic analysis of the cord blood revealed a karyotype of 46,XX in 40/40 cultured lymphocytes. The neonate was normal in growth and psychomotor development at 6 months of age. Interphase FISH analysis on uncultured urinary cells revealed 5% (1/20 cells) mosaicism for trisomy 12. ConclusionPrenatal diagnosis of mosaic trisomy 12 at amniocentesis should alert a clinically significant aneuploidy. Interphase FISH and aCGH on uncultured amniocytes are useful for rapid confirmation of low-level trisomy 12 mosaicism at repeated amniocentesis.

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

ObjectiveThis study aims at presenting prenatal diagnosis of mosaic trisomy 2 and reviewing the literature. Materials, Methods, and ResultsA 32-year-old woman underwent amniocentesis at 21 weeks of gestation because of abnormal maternal serum biochemistry. Amniocentesis revealed a karyotype of 47,XY,+2[1]/46,XY[21] in in situ cultures. The single colony with trisomy 2 had two metaphase cells, and both had the karyotype of 47,XY,+2. Repeated amniocentesis was performed at 23 weeks of gestation. Interphase fluorescence in situ hybridization (FISH) analysis on uncultured amniocytes using a 2q11.1-specific probe RP11-468G5 (spectrum green) showed three green signals in 11 of 47 uncultured amniocytes, indicating 23.4% mosaicism for trisomy 2. The cultured amniocytes had a karyotype of 46,XY[20 colonies]. Polymorphic DNA marker analysis excluded uniparental disomy 2. The woman underwent the third amniocentesis at 25 weeks of gestation. Interphase FISH analysis on uncultured amniocytes revealed 9.4% (5/53 cells) mosaicism for trisomy 2. The cultured amniocytes had a karyotype of 46,XY[30 colonies]. Prenatal ultrasound was normal. The parents decided to continue the pregnancy to term, and a 3316-g baby was delivered with no phenotypic abnormalities. Cord blood had a karyotype of 46,XY[40 cells]. Interphase FISH analysis on uncultured urinary cells revealed 8.2% (4/49 cells) mosaicism for trisomy 2. The neonate was normal in growth and psychomotor development at 6 months of age. ConclusionPrenatal diagnosis of a single colony with two or more cells with trisomy 2 at amniocentesis should alert a clinically significant aneuploidy, and interphase FISH on uncultured amniocytes is useful for rapid confirmation of low-level trisomy 2 mosaicism at amniocentesis. The abnormal cell line of trisomy 2 may disappear after long-term amniocyte cultures.

Prenatal diagnosis of mosaic trisomy 9

Prenatal diagnosis of mosaic trisomy 9

Prenatal diagnosis of mosaic trisomy 8: Clinical report and literature review

Objective To present prenatal diagnosis of mosaic trisomy 8 and to review the literature. Materials, Methods, and Results A 34-year-old woman underwent amniocentesis at 16 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 47,XY,+8[6]/46,XY[31]. Repeated amniocentesis at 21 weeks of gestation revealed a karyotype of 47,XY,+8[4]/46,XY[77]. Interphase fluorescence in situ hybridization analysis of uncultured amniocytes showed 25% (5/20) mosaicism for trisomy 8. Array comparative genomic hybridization (aCGH) and quantitative fluorescent polymerase chain reaction (QF-PCR) analyses of uncultured amniocytes revealed no genomic imbalance in chromosome 8. The result of QF-PCR excluded uniparental disomy 8. At 23 weeks of gestation, the woman underwent amniocentesis and cordocentesis at other hospitals. Amniocentesis revealed a karyotype of 47,XY,+8[6]/46,XY[10]. Cordocentesis revealed a karyotype of 47,XY,+8[1]/46,XY[29]. Level II ultrasound findings were unremarkable. The parents decided to continue the pregnancy. A 1373-g male baby was prematurely delivered at 29 weeks of gestation. The peripheral blood had a karyotype of 47,XY,+8[1]/46,XY[29]. The infant had normal growth and mental development at 4 months of age. Conclusion Fetuses with mosaic trisomy 8 are compatible with viability and can have a favorable outcome. QF-PCR and array comparative genomic hybridization have the limitation of detection of low-level mosaicism. We suggest that in instances of repeated amniocentesis for confirmation of mosaic trisomy 8, follow-up investigations should include interphase fluorescence in situ hybridization studies on uncultured amniocytes, uniparental disomy tests, and detailed ultrasound examinations.

Prenatal diagnosis of mosaic trisomy 2: Discrepancy between molecular cytogenetic analyses of uncultured amniocytes and karyotyping of cultured amniocytes in a pregnancy with severe fetal intrauterine growth restriction

Prenatal diagnosis of mosaic trisomy 2: Discrepancy between molecular cytogenetic analyses of uncultured amniocytes and karyotyping of cultured amniocytes in a pregnancy with severe fetal intrauterine growth restriction

Mosaic trisomy 4: Long-term outcome on the first reported liveborn

In a previous report, we described the first liveborn with trisomy 4 mosaicism [Marion et al. (1990) Am J Med Genet 37:362-365]. To our knowledge, since our original report, there have been only four additional reports of a prenatal diagnosis of mosaic trisomy 4 resulting in a liveborn child [Hsu et al. (1997) Prenat Diag 17:201-242; Kuchinka et al. (2001) Prenat Diag 21:36-39; Wieczorek et al. (2003) Prenat Diag 23:128-133; Zaslav et al. (2000) Am J Med Genet 95:381-384]. Three of the more recent reports lacked confirmation of the mosaicism in tissue samples collected from the child after delivery, and likely represent cases of confined placental mosaicism. We recently examined our original patient, N.J., in an effort to provide long-term follow-up. N.J. is currently 14-years-old, and is enrolled in both special education and mainstream eighth grade classes at a local public middle school. Although she generally scores below average on standardized intellectual tests, her verbal skills and social interactions are more age appropriate. Our initial report described abnormalities of N.J.'s right hand and right ear, for which several reconstructive surgeries have been performed. A current medical concern is her entrance into puberty, as menarche has not yet occurred, and asymmetrical breast development is present. Overall, N.J. has developed into a generally healthy adolescent with low-normal intellect. This report demonstrates the importance of long-term follow-up in providing accurate counseling for rare chromosomal disorders.

Prenatal diagnosis of mosaic trisomy 20 in New Zealand.

Mosaic trisomy 20 is not an uncommon finding on amniocentesis or CVS. Unlike other mosaic aneuploidies it is a relatively benign abnormality which, along with a lack of long-term follow-up of cases, has led to uncertainty when counselling parents. We aimed to identify known mosaic trisomy 20 pregnancies in New Zealand in the last 10 years and document their outcome. Retrospective database review with prospective clinical follow-up. Cases were identified from the databases of the two clinical genetic services, as well as the four regional cytogenetics laboratories. Medical records were reviewed and where patients were available they were offered follow-up. Fourteen cases were identified (13 on amniocentesis, one on CVS), all with low levels of mosaicism (8-50%). In 12 cases, the children were physically and developmentally normal, with the longest follow-up being 10 years. Minor anomalies were noted in two cases. There were no major malformations noted in any of the cases and where repeat karyotypes were performed on blood or urine cytology these were normal. This series confirms a much lower incidence of phenotypic abnormalities associated with mosaic trisomy 20 compared to other forms of mosaic aneuploidy. Attempts to predict which of these pregnancies will have poor outcomes have not proven to be reliable. We recommend that, if a detailed anatomy scan is normal, parents be counselled that the risk of abnormality is less than 10%. Further tests should be performed only on the basis of a clinical indication.

Prenatal diagnosis of mosaic trisomy 8 in a fetus with normal nuchal translucency thickness and reversed end‐diastolic ductus venosus flow

We report a case of the prenatal diagnosis of trisomy 8 in a fetus presenting with normal nuchal translucency of 0.8 mm and reversed end-diastolic ductus venosus blood flow at a routine first-trimester scan at 11 weeks of gestation. No structural abnormalities were detected by the ultrasound scan. Karyotyping by chorionic villus sampling led to the diagnosis of mosaic trisomy 8, which was confirmed by fluorescent in-situ hybridization on fetal tissue samples.

Prenatal diagnosis of mosaic trisomy 8 with investigations of the extent and origin of trisomic cells

A case of trisomy 8 mosaicism, which presented at obstetric ultrasound at 18 weeks' gestation with a distended bladder and absence of amniotic fluid, is described. Analysis of DNA microsatellite polymorphisms indicates that the trisomic cell line most likely arose as the result of a post-fertilization non-dysjunction event in early development of a chromosomally normal pre-implantation embryo. The distribution of normal and trisomy 8 cells suggests that in this pregnancy there has been either uneven allocation of abnormal cells to the extra-embryonic mesoderm, or selection against the proliferation of trisomic cells in trophoblast derived cell lineages. This prenatal detection of trisomy would not have been possible if only analysis of direct preparations had been undertaken.

Prenatal diagnosis of mosaic trisomy 8 with investigations of the extent and origin of trisomic cells

Prenatal diagnosis of mosaic trisomy 8 with investigations of the extent and origin of trisomic cells