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Objective:
To present prenatal diagnosis and molecular cytogenetic characterization of mosaicism for a small supernumerary marker chromosome (sSMC) derived from ring chromosome 2 [r(2)].
Methods and results:
A 35-year-old woman underwent amniocentesis at 17 weeks of gestation, because of advanced maternal age. Amniocentesis revealed a de novo ri...
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Objective: We present prenatal diagnosis and molecular genetic analysis of mosaic trisomy 17 and a review of the literature of mosaic trisomy 17 at amniocentesis.
Materials and Methods: A 42-year-old woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age, which revealed a karyotype of 47,XX,+17[4]/46,XX[17]. Prenata...
Objective:
We present a familial 21q22.3 microduplication in a fetus associated with prenatally detected congenital heart defects (CHD).
Case report:
A 38-year-old woman underwent amniocentesis at 22 weeks of gestation because of sonographic findings of double outlet of right ventricle, ventricular septal defect and transposition of great artery...
Objective
We describe a rare case of “pure” 8q duplication diagnosed prenatally by conventional karyotyping, that was further characterized by array comparative genomic hybridization (aCGH).
Case report
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Objective
We present prenatal diagnosis and molecular cytogenetic characterization of Wolf–Hirschhorn syndrome (WHS) in a fetus with facial cleft and preaxial polydactyly.
Materials and methods
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Objective:
We present prenatal diagnosis of a 2p16.1-p15 duplication associated with familial intellectual disability, and we discuss the genotype-phenotype correlation.
Case report:
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Citations
... We previously reported prenatal diagnosis and molecular cytogenetic characterization of mosaicism for a small supernumerary marker chromosome (sSMC) derived from chromosome 2 [1,2]. Here, we present an additional case derived from 2q11.1-q12.1 associated with fetal bilateral radial dysplasia. ...
Objective
We present prenatal diagnosis and molecular cytogenetic characterization of mosaicism for a small supernumerary marker chromosome (sSMC) derived from 2q11.1-q12.1 associated with fetal bilateral radial dysplasia.
Case report
A 27-year-old woman underwent amniocentesis at 18 weeks of gestation because of club hands on fetal ultrasound. The internal organs of the fetus were normal. Amniocentesis revealed a karyotype of 47,XY,+mar [13]/46,XY [11]. The parental karyotypes were normal. Simultaneous array comparative genomic hybridization (aCGH) analysis of the DNA extracted from uncultured amniocytes revealed the result of arr 2q11.1q12.1 (95,529,039–102,825,556) × 3.0 [GRCh37 (hg19)]. The pregnancy was terminated at 20 weeks of gestation, and a malformed fetus was delivered with isolated bilateral radial dysplasia. The cord blood had a karyotype of 47,XY,+mar[24]/46,XY[16]. Polymorphic DNA marker analysis of the DNAs extracted from umbilical cord and parental bloods excluded uniparental disomy for chromosome 2. Metaphase fluorescence in situ hybridization analysis confirmed an sSMC derived from chromosome 2q11.1-q12.1 in cultured amniocytes.
Conclusion
High-level mosaicism for an sSMC derived from chromosome 2q11.1-q12.1 can be associated with fetal abnormalities.
... Recently, chromosome microarray analysis (CMA) is a main diagnostic method and the "gold standard" for chromosome micro-deletion or micro-duplication diagnosis. It can not only provide a high resolution genome-wide screening for the CNV diagnosis but also detect the increase or decrease of the unknown genomic DNA fragments [8]. Thus it is of significance to discovery and identification of gene-related diseases. ...
Objective:
To assess the accuracy of copy number variations (CNVs) detection by non-invasive prenatal testing (NIPT) in addition to its routine targets and clinical significance of such CNVs for the reduction of fetuses born with chromosomal microdeletion/duplication syndromes.
Methods:
From October 2014 to October 2015, 14 235 pregnant women volunteered to participate in the study. Fifteen cases detected with chromosomal CNVs by the NIPT decided to undergo prenatal diagnostic procedures including amniocentesis, G-banded karyotyping and chromosomal microarray analysis (CMA). All such cases were routinely followed up after birth.
Results:
Among the 14 235 subjects underwent NIPT, 18 cases were detected with Down syndrome, 4 with trisomy 18, and 2 with trisomy 13, in addition with 24 cases of CNVs. For the latter, 15 (including 11 cases with microdeletions and 4 cases with microduplications) participated in further prenatal diagnosis. In 13 cases (86.7%), the results of CMA were consistent with those of NIPT. On the other hand, only 7 out of the 15 cases showed a positive result with karyotyping, suggesting a rather high rate of missed diagnosis (46.2%). Of note, karyotyping has identified partial inversion of chromosome 9 in one case.
Conclusion:
As a screening tool, NIPT has a high accuracy for the detection of CNVs. However, as this method is still under improvement, it is more of a reminder rather than a diagnostic tool with full capability.
... We previously reported prenatal diagnosis and molecular cytogenetic characterization of mosaicism for a small supernumerary marker chromosome 15 [sSMC(15) ] without phenotypic abnor- malities [1]. In this report, we additionally present a case with an sSMC(15) that was confirmed to be the inverted duplication of proximal chromosome 15 [inv dup(15)] and was associated with the inv dup(15) syndrome. ...
Objective: To present molecular cytogenetic characterization of an inverted duplication of proximal chromosome 15 [inv dup(15)] presenting as a small supernumerary marker chromosome (sSMC) associated with the inv dup(15) syndrome.
Case Report: A 35-year-old woman underwent amniocentesis because of advanced maternal age at 27 weeks of gestation, which revealed an sSMC that was confirmed by fluorescence in situ hybridization (FISH) to be derived from chromosome 15. Prenatal ultrasound findings were unremarkable. A 3434-g male baby was delivered at term with no phenotypic abnormalities. The cord blood analysis revealed a bisatellited dicentric inv dup(15). When followed up at 21 years of age, the proband manifested hypotonia, ataxic gait, developmental delay, intellectual disability, epilepsy, poor speech, and autism consistent with the inv dup(15) syndrome. Array comparative genomic hybridization of the peripheral blood revealed arr 15q11.1q13.2 (20,686,219–30,390,043) × 4, 15q13.2q13.3 (30,390,043–32,445,226) × 3. Conventional cytogenetic analysis of the peripheral blood revealed a karyotype of 47,XY,+inv dup(15)(pter→q13::q13→pter). Quantitative fluorescent polymerase chain reaction analysis showed a maternal origin of the inv dup(15) chromosome. FISH analysis confirmed an inv dup(15) chromosome.
Conclusion: Molecular cytogenetic techniques are useful for rapid diagnosis of an inv dup(15) chromosome associated with the inv dup(15) syndrome.
... In a traditional prenatal diagnosis program, when genetic aberrations are suspected in a fetus' genome, invasive procedures, such as chorionic villus sampling (CVS), amniocentesis, or percutaneous umbilical cord blood sampling (PUBS)/cordocentesis, are used to provide fetal samples for genetic detection by well-established genetic analysis techniques, such as G-band karyotyping, fluorescence in situ hybridization (FISH), quantitative fluorescence PCR (QF-PCR), or chromosomal microarray analysis (CMA, including aCGH and SNP arrays) [8,[10][11][12]. These programs did not change until 1997, when the discovery of free fetal DNA (ffDNA) in maternal plasma promoted the development of noninvasive prenatal diagnosis [13]. ...
... However, FISH detects only its intended targets and may provide no information regarding additional abnormalities [12]. CMA provides high-resolution genome-wide screening of the CNVs, and it could be used to detect the gains and losses of genomic DNA fragments even when the fragments are unknown and have discrete genomic loci [8,10]. Therefore, CMA is widely used in prenatal diagnosis and other clinical diagnoses. ...
... Therefore, CMA is widely used in prenatal diagnosis and other clinical diagnoses. CMA needs only a few micrograms of fetal genomic DNA for prenatal diagnosis, but DNA samples cannot be obtained unless an invasive procedure is performed [10,11]. NIPT was initially used in the prediction of T13, T18, T21 and sex chromosome abnormalities in prenatal diagnosis studies. ...
Microdeletions of chromosome 13q31.1 are relatively rare. These types of deletions may cause different genetic effects on genotypes and/or phenotypes. There are several ways to detect microdeletions; noninvasive prenatal testing (NIPT) is the newest detection method. In this study, we aimed to investigate the genetic effects of a 13q31.1 microdeletion detected by NIPT and to reconfirm the feasibility of this procedure in predicting sub-chromosomal copy number variations (CNVs). The 13q31.1 microdeletion, which has previously been described as a disease-associated fragment, was detected by NIPT in a pregnant woman. To validate the finding and to explain the origin of this sub-chromosomal CNV, we collected fetal amniotic fluid and parental blood samples and tested the samples using array-based comparative genomic hybridization (aCGH). Karyotype analysis was performed on all of the samples to rule out balanced or mosaic anomalies. The aCGH results confirmed the NIPT findings. We detected the same type of microdeletion in the fetus and the mother via aCGH. The mother had a normal phenotype; therefore, in a post-test genetic counseling session, we predicted a normal phenotype for the fetus. After delivery, the normal phenotype of the newborn confirmed our prediction. Based on the present study, this 13q31.1 microdeletion may be considered as a chromosomal polymorphism. This study also reconfirmed the feasibility of obtaining a molecular karyotype of a fetus via NIPT.
Objective
We present prenatal diagnosis and molecular cytogenetic characterization of a small supernumerary marker chromosome (sSMC) derived from chromosome 15 in a pregnancy associated with recurrent Down syndrome.
Case report
A 33-year-old, gravida 4, para 2, woman underwent amniocentesis at 16 weeks of gestation because of a previous child with Down syndrome and a karyotype of 46,XY,der(14;21)(q10; q10),+21. In this pregnancy, amniocentesis revealed a karyotype of 47,XX,+21[12]/48,XX,+21,+mar[3]. The parental karyotypes were normal. The pregnancy was terminated, and a malformed fetus was delivered with characteristic craniofacial appearance of Down syndrome and hypoplastic middle phalanx of the fifth fingers. The placenta had a karyotype of 47,XX,+21[37]/48,XX,+21,+mar[3]. The umbilical cord had a karyotype of 47,XX,+21[38]/48,XX,+21,+mar[2]. In addition to trisomy 21, array comparative genomic hybridization (aCGH) on the DNA extracted from umbilical cord revealed 40∼50% mosaicism for a 2.604-Mb duplication of 15q25.2–q25.3, or arr 15q25.2q25.3 (83,229,665–85,834,131) × 2.4 [GRCh37 (hg19)] encompassing 19 Online Mendelian Inheritance in Man (OMIM) genes. Quantitative fluorescent polymerase chain reaction (QF-PCR) using the DNAs extracted from cultured amniocytes and parental bloods revealed maternal origin of the sSMC(15) and the extra chromosome 21.
Conclusion: aCGH is useful for identification of the nature of sSMC, and QF-PCR is useful for determination of the parental origin of the aberrant chromosomes.
The aim of the current review is to report a-CGH abnormalities identified in fetuses with prenatally diagnosed fetal malformations in whom a normal karyotype was diagnosed with conventional cytoge- netic analysis.
A systematic electronic search of databases (PubMed/Medline, EMBASE/SCOPUS) has been conducted from inception to May, 2017. Bibliographic analysis has been performed according to PRISMA statement for review. The following keywords were used: ‘array-CGH’ and ‘fetal malformations” and “prenatal diagnosis”; alternatively, “microarray”, “oligonucleotide array”, “molecular biology”, “antenatal di- agnostics”, “fetal diagnostics”, “congenital malformations” and “ultrasound” were used to capture both “a-CGH” and “prenatal”.
One-hundred and twelve fetuses with prenatally diagnosed fetal malformations with normal kar- yotyping and a-CGH abnormalities detected are described. Single or multiple microarray abnormalities diagnosed have been classified in relation to different organ/system affected. The most frequent a-CGH abnormalities were detected in cases of congenital heart diseases (CDHs), multiple malformations and central nervous system (CNS) malformations. Maternal or paternal carrier-state was seen in 19.64% (22/ 112), of cases while the number of reported de novo mutations accounted for 46.42% (52/112) of all CNVs microarray abnormalities. Array-comparative genomic hydridization (a-CGH) may become an integral and complemantary genetic testing when fetal malformations are detected prenatally in fetuses with normal cytogenetic karyotype. In addition, a-CGH enables the identification of CNVs and VOUS and improves the calculation of recurrent risk and the genetic counseling.
Objective: We present prenatal diagnosis and molecular cytogenetic characterization of mosaicism for a small supernumerary marker chromosome (sSMC) derived from chromosome 2.
Case Report: A 42-year-old woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 47,XY,+mar[10]/46,XY[12]. The parental karyotypes were normal. Array comparative genomic hybridization analysis of the DNA extracted from cultured amniocytes revealed no genomic imbalance. Spectral karyotyping analysis failed to identify the sSMC. Metaphase fluorescence in situ hybridization analysis using the satellite probes CEP1/5/19, CEP2, CEP3, CEP4, CEP6, CEP7, CEP8, CEP9, CEP10, CEP12, CEP13/21, CEP14/22, CEP15, CEP16, and CEP20 revealed a result of 47,XY,+mar .ish der(2)(D2Z+)[10]. The sSMC was derived from the α satellite of chromosome 2. Polymorphic DNA marker analysis using the markers specific for chromosome 2 on the DNAs extracted from cultured amniocytes and parental bloods excluded uniparental disomy 2. At 39 weeks of gestation, a healthy 3394-g male baby was delivered with no phenotypic abnormality. The cord blood had a karyotype of 47,XY,+mar[21]/46,XY[19].
Conclusion: Array comparative genomic hybridization and spectral karyotyping may fail to detect an sSMC derived from α satellite, which needs satellite probes for confirmation.
Côté et al. [1981] suggested that ring chromosomes with or without deletions share a common pattern of phenotypic anomalies, regardless of which chromosome is involved. The phenotype of this 'general ring syndrome' consists of growth failure without malformations, few or no minor anomalies, and mild to moderate mental retardation. We reconsidered the ring chromosome 2 case previously published by Côté et al. [1981], and we characterized it by array CGH, polymorphic markers as well as subtelomere MLPA and FISH analysis. A terminal deletion (q37.3qter) of maternal origin of the long arm of the ring chromosome 2 was detected and confirmed by all the above-mentioned methods. Ring chromosome 2 cases are exceedingly rare. Only 18 cases, including the present one, have been published so far, and our patient is the longest reported survivor, with a 35-year follow-up, and the third case characterized by array-CGH analysis. © 2015 S. Karger AG, Basel.
We present prenatal diagnosis and molecular cytogenetic analysis of mosaic small supernumerary marker chromosome 1 [sSMC(1)]. We review the literature of sSMC(1) at amniocentesis and chromosome 1p21.1-p12 duplication syndrome. We discuss the genotype-phenotype correlation of the involved genes of ALX3, RBM15, NTNG1, SLC25A24, GPSM2, TBX15 and NOTCH2 in this case.
