Prenatal diagnosis and molecular cytogenetic characterization of mosaicism for a small supernumerary marker chromosome derived from ring chromosome 2

ObjectiveTo 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 ResultsA 35-year-old woman underwent amniocentesis at 17 weeks of gestation, because of advanced maternal age. Amniocentesis revealed a de novo ring-shaped sSMC in 11 of 23 colonies of cultured amniocytes. Repeated amniocenteses were made. The sSMC was characterized by array comparative genomic hybridization (aCGH), interphase fluorescence in situ hybridization (FISH) and quantitative fluorescent polymerase chain reaction (QF-PCR) on uncultured amniocytes. In uncultured amniocytes, aCGH showed a 39.49-Mb genomic gain in chromosome 2 encompassing 2q11.2→q21.2, interphase FISH revealed a mosaic level of 52% (52/100 cells), and QF-PCR manifested a diallelic pattern for chromosome 2, with gene dosage increase in the paternal allele of proximal 2q-specific DNA markers. In cultured amniocytes, the sSMC was characterized by metaphase FISH, spectral karyotyping (SKY) and multicolor banding (MCB) to contain the centromere and proximal 2q, and the karyotype was 47,XX,+r(2)(p11.1q21.2)[14]/46,XX[11]. The pregnancy was terminated. The fetus postnatally manifested facial dysmorphisms. Postnatal cytogenetic analyses revealed the karyotypes of 47,XX,+r(2)[12]/46,XX[28] in cord blood, 47,XX,+r(2)[7]/46,XX[33] in umbilical cord, 47,XX,+r(2)[13]/47,XX,+idic r(2)[3]/46,XX[24] in placenta and 47,XX,+r(2)[8]/47,XX,+idic r(2)[1]/46,XX[31] in amnion.ConclusionMolecular cytogenetic techniques such as aCGH, interphase FISH and QF-PCR on uncultured amniocytes, and SKY, MCB and metaphase FISH on cultured amniocytes are useful for characterization of the nature of a prenatally detected sSMC.     

Prenatal diagnosis and molecular cytogenetic characterization of mosaicism for a small supernumerary marker chromosome derived from chromosome 3

ObjectiveWe present prenatal diagnosis and molecular cytogenetic characterization of a small supernumerary marker chromosome (sSMC) derived from chromosome 3.Case reportA 36-year-old woman underwent amniocentesis at 19 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 47,XX,+mar[6]/46,XX[18]. The mother's karyotype was 47,XX,+mar[4]/46,XX[46]. The father's karyotype was 46.XY. Array comparative genomic hybridization (aCGH) analysis of uncultured amniocytes revealed a result of arr 3q11.1q12.1 (93,575,285–98,956,687) × 2–3 [GRCh37 (hg19)]. Prenatal ultrasound findings were unremarkable. The parents elected to continue the pregnancy, and a 2470-g female baby was delivered at 37 weeks of gestation without phenotypic abnormalities. The cord blood had a karyotype of 47,XX,+mar[8]/46,XX[32]. aCGH analysis of cord blood revealed a result of arr 3q11.1q11.2 (93,649,973–97,137,764) × 2.4 [GRCh37 (hg19)] with a log2 ratio of 0.25 and a 30–40% mosaicism for 3.488-Mb dosage increase in 3q11.1-q11.2 encompassing four [Online Mendelian Inheritance in Man (OMIM)] genes of PROS1, ARL13B, NSUN3 and EPHA6. Metaphase fluorescence in situ hybridization (FISH) analysis confirmed 30% (6/20 cells) mosaicism for the sSMC(3) in the blood lymphocytes.ConclusionaCGH and FISH analyses are useful for perinatal investigation of a prenatally detected sSMC.     

Prenatal diagnosis and molecular cytogenetic characterization of mosaicism for a small supernumerary marker chromosome derived from chromosome 11

Objective

We present prenatal diagnosis and molecular cytogenetic characterization of a small supernumerary marker chromosome (sSMC) derived from chromosome 11.

Prenatal diagnosis and molecular cytogenetic characterization of mosaicism for a small supernumerary marker chromosome derived from chromosome 16

Objective

We present prenatal diagnosis and molecular cytogenetic characterization of a small supernumerary marker chromosome (sSMC) derived from chromosome 16.

Prenatal diagnosis and molecular cytogenetic characterization of mosaicism for a small supernumerary marker chromosome derived from chromosome 2

Objective

We present prenatal diagnosis and molecular cytogenetic characterization of mosaicism for a small supernumerary marker chromosome (sSMC) derived from chromosome 2.

Prenatal diagnosis and molecular cytogenetic characterization of mosaicism for a small supernumerary marker chromosome derived from chromosome 21q11.2-q21.1 and a literature review

Objective

We present prenatal diagnosis and molecular cytogenetic characterization of mosaicism for a small supernumerary marker chromosome (sSMC) derived from chromosome 21q11.2-q21.1, and we review the literature of an sSMC(21) with a duplication of 21q11.2-q21.1.

Prenatal diagnosis and molecular cytogenetic characterization of a small supernumerary marker chromosome derived from inv dup(15)

ObjectiveWe present prenatal diagnosis and molecular cytogenetic characterization of an inverted duplication of proximal chromosome 15 [inv dup(15)] presenting as a small supernumerary marker chromosome (sSMC) at amniocentesis associated with concomitant microduplication of 8q22.1.Materials and methodsA 39-year-old woman underwent amniocentesis at 16 weeks of gestation because of advanced maternal age, and the result was 47, XY, +mar dn. The woman requested for repeat amniocentesis at 20 weeks of gestation. Array comparative genomic hybridization (aCGH), fluorescence in situ hybridization (FISH), quantitative fluorescent polymerase chain reaction (QF-PCR) and DNA methylation analysis were applied to determine the nature of the sSMC.Results: aCGH on the uncultured amniocytes revealed the result of arr 8q22.1 (93,918,763–96,618,539) × 3.0, arr 15q11.2q13.2 (22,765,628–30,658,876) × 4.0, arr 15q13.2q13.3 (30,653,877–32,509,926) × 3.0 [GRCh37 (hg19)]. Interphase FISH analysis using RP11-34H12 [15q13.2; Texas Red, 30,709,033–30,893,021 (hg19)] on 100 uncultured amniocytes showed that 38 cells had three signals, 45 cells had four signals and 27 cells had two signals. The parental bloods had normal aCGH results. The karyotype of cultured amniocytes was 47, XY, +inv dup(15) (pter→q13::q13→pter) which was confirmed by metaphase FISH analysis. No informative markers could be found in QF-PCR analysis. DNA methylation analysis on cord blood confirmed a maternal origin of the 15q11-q13 gene dosage increase with a result of 15q11.2 SNRPN DNA hypermethylation. Postnatal cytogenetic analysis on cord blood, umbilical cord and placenta showed the results consistent with the prenatal diagnosis.ConclusionMolecular cytogenetic techniques are useful for rapid diagnosis of an inv dup(15) chromosome presenting as an sSMC at amniocentesis.     

Prenatal diagnosis and molecular cytogenetic characterization of a familial small supernumerary marker chromosome derived from the acrocentric chromosome 14/22

ObjectiveWe present prenatal diagnosis and molecular cytogenetic characterization of a familial small supernumerary marker chromosome (sSMC) derived from the acrocentric chromosome 14/22.Case reportA 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 47,XY,+mar. Prenatal ultrasound was unremarkable. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed no genomic imbalance. Cytogenetic analysis of the parental bloods revealed a karyotype of 47,XY,inv (9) (p12q13),+mar in the father and a karyotype of 46, XX in the mother. The sSMC was investigated by fluorescence in situ hybridization (FISH) analysis on cultured amniocytes using the CEP 13/21 α-satellite specific gene probe labeled with fluorescein isothiocyanate (FITC) fluorophore and the CEP 14/21 α-satellite specific gene probe labeled with Texas Red fluorophore (Cytocell Inc.). The result showed that the sSMC was derived from the chromosome 14/22, or+mar.ish dic (14/22) (D13Z1/D21Z1-, D14Z1/D22Z1+)[20]. A healthy male baby was delivered at term with no phenotypic abnormality. Quantitative fluorescent polymerase chain reaction (QF-PCR) analysis on parental bloods and the child's peripheral blood was used to exclude uniparental disomy (UPD) (14) and UPD(22).ConclusionFISH analysis is useful for the determination of an sSMC derived from an acrocentric chromosome under the circumstance of no genomic imbalance at amniocentesis. QF-PCR analysis is useful for excluding the possible associated UPD.     

Prenatal diagnosis and molecular cytogenetic characterization of mosaicism for a small supernumerary marker chromosome derived from 2q11.1-q12.1 associated with fetal bilateral radial dysplasia

ObjectiveWe 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 reportA 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.ConclusionHigh-level mosaicism for an sSMC derived from chromosome 2q11.1-q12.1 can be associated with fetal abnormalities.     

Prenatal diagnosis and molecular cytogenetic characterization of a small supernumerary marker chromosome derived from chromosome 15 in a pregnancy associated with recurrent Down syndrome

ObjectiveWe 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 reportA 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.     

Molecular cytogenetic characterization of mosaicism for a small supernumerary marker chromosome derived from chromosome 8 associated with congenital hypoplasia of the tongue and review of the literature

ObjectiveTo present molecular cytogenetic characterization of mosaic supernumerary ring chromosome 8 which has trisomy of a region of chromosome 8p12-q21.13 associated with congenital hypoplasia of the tongue and review of the literature.Case reportA 27 year-old woman presented with congenital hypoplasia of the tongue. The chromosome karyotype of peripheral blood lymphocytes was detected by conventional cytogenetic analysis. The genome copy number variations were detected by SNP array. Conventional cytogenetic analysis of the peripheral blood revealed a karyotype of 47,XX,+mar[60]/46,XX[40]. SNP array revealed that there was a duplication of 45.2 Mb at arr[hg19] 8p12q21.13(36,013,636–81,263,140) × 2–3.ConclusionWith this study a patient involving mosaic trisomy 8p12-q21.13 along with clinical properties, is described and compared to previously reported cases involving a small supernumerary marker chromosome (sSMC) derived from chromosome 8.     

Prenatal diagnosis of a de novo supernumerary marker derived from chromosome 16.

Marker chromosomes are supernumerary chromosomes of unknown origin and are seldom found in prenatal diagnosis. Application of fluorescent in situ hybridization (FISH) allows the identification of the chromosomal origin of markers. Estimation of the risk of an abnormal phenotype outcome can be enabled by collecting data on phenotypes associated with markers of the same chromosomal origin. So far only very few cases of prenatal diagnosis of de novo supernumerary markers derived from chromosome 16 have been reported. Here the prenatal diagnosis of a de novo supernumerary marker chromosome 16 is described and the relevant literature discussed.