Detection of de novo del(18)(q22.2) and a familial of 15q13.2-q13.3 microduplication in a fetus with congenital heart defects

ObjectiveWe present detection of de novo del(18)(q22.2) and a familial 15q13.2-q13.3 microduplication in a fetus with congenital heart defects (CHD).Case reportA 27-year-old, primigravid woman was referred for genetic counseling because of fetal CHD. Prenatal ultrasound at 17 weeks of gestation revealed pericardial effusion, cardiomegaly and a large ventricular septal defect. The pregnancy was subsequently terminated at 18 weeks of gestation, and a 192-g female fetus was delivered with facial dysmorphism. Cytogenetic analysis of the umbilical cord revealed a karyotype of 46,XX,del(18)(q22.2). The parental karyotypes were normal. Array comparative genomic hybridization (aCGH) of the placental tissue revealed a 2.08-Mb 15q13.2-q13.3 microduplication encompassing KLF13 and CHRNA7, and a 10.74-Mb 18q22.2-q23 deletion encompassing NFATC1. The phenotypically normal father carried the same 2.08-Mb 15q13.2-q13.3 microduplication. Polymorphic DNA marker analysis confirmed a paternal origin of the distal 18q deletion.ConclusionPrenatal diagnosis of CHD should include a complete genetic study of the embryonic tissues, and the acquired information is useful for genetic counseling.     

Mosaic Xq duplication,or 46,X,der(X)dup(X)(q22.1q22.2)dup(X)(q25q22.3)/ 46,XX at amniocentesis in a pregnancy with a favorable outcome

ObjectiveWe present mosaic Xq duplication, or 46,X,der(X)dup(X)(q22.1q22.2)dup(X)(q25q22.3)/46,XX at amniocentesis in a pregnancy with a favorable outcome.Case ReportA 40-year-old woman underwent amniocentesis at 16 weeks of gestation because of advanced maternal age. Amniocentesis revealed a result of 46,X,der(X)dup(X)(q22.1q22.2)dup(X)(q25q22.3)[7]/46,XX[20]. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed the result of arr (1–22, X) × 2. Cytogenetic analysis on maternal blood revealed a karyotype of 46,XX. At 22 weeks of gestation, she underwent repeat amniocentesis which revealed a karyotype of 46,XX in 22/22 colonies of cultured amniocytes and an aCGH result of (1–22, X) × 2 in the uncultured amniocytes. Prenatal ultrasound findings were unremarkable. The parents decided to continue the pregnancy, and a healthy female baby was delivered at 39 weeks of gestation with a body weight of 3510 g and a body length of 49 cm. The cord blood had a karyotype of 46,X,der(X)dup(X)(q22.1q22.2)dup(X)(q25q22.3)[3]/46,XX[37]. At age two months, interphase fluorescence in situ hybridization (FISH) analysis on buccal mucosal cells showed Xq duplication signals in 1.25% (1/80 cells), compared with 0% (0/90 cells) in the normal control. At age nine months, the neonate had normal physical and psychomotor development. Her body weight was 9.6 Kg (85th - 97th centile), and body length was 72 cm (50th - 85th centile). Cytogenetic analysis of peripheral blood revealed a karyotype of 46,X,der(X)dup(X) (q22.1q22.2)dup(X)(q25q22.3)[1]/46,XX[39]. Interphase FISH analysis on 100 buccal mucosal cells revealed no abnormal signal.ConclusionIn case of mosaicism for an Xq duplication with a normal euploid cell line at amniocentesis, the in-vitro culture process of amniocytes may cause over-estimation of the mosaic level for the aberrant chromosome because of culture artifacts, and the abnormal cell line can decline after birth.     

Prenatal diagnosis and molecular cytogenetic characterization of partial dup(18q)/del(18p) due to a paternal pericentric inversion 18 in a fetus with multiple anomalies

ObjectiveWe present prenatal diagnosis of rec(18)dup(18q)inv(18)(p11.2q21.2)pat owing to paternal pericentric inversion in a fetus.Case reportA 37-year-old woman was diagnosed with multiple anomalies on a prenatal ultrasound scan at 17 weeks and 5 days of gestation. She underwent amniocentesis at 20 weeks and 2 days. Conventional karyotyping of amniocyte showed 46, XX, der(18). She was thus referred for genetic counseling; cytogenetic analysis revealed a 46, XY karyotype, inv(18)(p11.2q21.2), of the father. Therefore, based on the results of the father, the fetal karyotype was defined as 46, XX, rec(18)dup(18q)inv(18)(p11.2q21.2)pat. Array comparative genomic hybridization of amniocytes to obtain specific information showed a 3-Mb deletion of 18p11.31p11.32 (136227_3100353)x1 and a 23.7-Mb duplication of 18q21.31-q23 (54222717_77957375) × 3.ConclusionMaternal serum screening produces normal results for 18p-/18q+ syndrome, but it can be diagnosed by fluorescent in situ hybridization, quantitative-fluorescent polymerase chain reaction, or array comparative genomic hybridization test by observing abnormal findings on ultrasound.     

Inv dup del(10p): Prenatal diagnosis and molecular cytogenetic characterization

ObjectiveWe present molecular cytogenetic characterization of prenatally detected inverted duplication and deletion of 10p [inv dup del(10p)].Case reportA 39-year-old, primigravid woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a derivative chromosome 10 with additional material at the end of the short arm of one chromosome 10. Simultaneous array comparative genomic hybridization (aCGH) analysis revealed the result of arr 10p15.3 (136,361–451,013) × 1, 10p15.3p12.1 (536,704–25,396,900) × 3 [GRCh37 (hg19)] with a 0.31-Mb deletion of 10p15.3 encompassing ZMYND11 and DIP2C, and a 24.86-Mb duplication of 10p15.3p12.1. The pregnancy was subsequently terminated, and a female fetus was delivered with facial dysmorphism. Postnatal aCGH analysis showed that the umbilical cord had the same result as that of amniotic fluid, whereas the placenta had only the deletion of 10p15.3. Fluorescence in situ hybridization (FISH) analysis of the cord blood confirmed inverted duplication and deletion of 10p. The cord blood had a karyotype of 46,XX,der(10) del(10) (p15.3)dup(10) (p15.3p12.1)dn. Polymorphic DNA marker analysis confirmed a maternal origin of the chromosome 10 aberration.ConclusionPrenatal diagnosis of inv dup del(10p) with haploinsufficiency of ZMYND11 should include a genetic counseling of mental retardation and chromosome 10p15.3 microdeletion syndrome. aCGH, FISH and polymorphic DNA marker analysis are useful for perinatal investigation of inv dup del(10p).     

Prenatal diagnosis and molecular cytogenetic characterization of a de novo interchromosomal insertion of ins(1;8)(p22.1;q22q23)

ObjectiveWe present prenatal diagnosis and molecular cytogenetic characterization of a de novo interchromosomal insertion of ins(1; 8)(p22.1; q22q23) at amniocentesis.Case reportA 34-year-old woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age. Conventional cytogenetic analysis revealed a chromosome 1p22.1 interstitial duplication and a chromosome 8q22-q23 interstitial deletion. The parental karyotypes were normal. Array comparative genomic hybridization (aCGH) analysis using the DNA extracted from cultured amniocytes revealed no genomic imbalance. Metaphase fluorescence in situ hybridization (FISH) analysis on cultured amniocytes showed an interchromosomal insertion of ins(1; 8)(p22.1; q22q23) or ins(1; 8) (1pter→1p22.1::8q23→8q22::1p22.1→1qter; 8pter→8q22::8q23→8qter). The long arm of chromosome 8 between bands 8q22 and 8q23 had been directly inserted into the short arm of chromosome 1 at band 1p22.1. The karyotype was 46,XY,ins(1; 8)(p22.1; q22q23) or 46,XY,ins(1; 8)(1pter→1p22.1::8q23→8q22::1p22.1→1qter; 8pter→8q22::8q23→8qter). After genetic counseling, the parents decided to continue the pregnancy. A phenotypically normal male baby was delivered at term.ConclusionFISH and aCGH are useful for genetic counseling and molecular cytogenetic characterization of a de novo interchromosomal insertion detected by amniocentesis.     

Prenatal diagnosis of trisomy 18p and distal 21q22.3 deletion

OBJECTIVES: To present the perinatal findings and molecular cytogenetic analysis of concomitant trisomy 18p (18p11.2-->pter) and distal 21q22.3 deletion. CASE AND METHODS: A 29-year-old woman, gravida 2 para 1, underwent amniocentesis at 17 weeks' gestation because she was a carrier of a balanced reciprocal translocation, 46,XX,t(18;21)(p11.2;q22.3). Cytogenetic analysis of the cultured amniocytes revealed a karyotype of 46,XX,der(21)t(18;21)(p11.2;q22.3). The fetus had a derivative chromosome 21 with an extra short arm of chromosome 18 attached to the terminal region of the long arm of chromosome 21. Level II sonograms did not find prominent structural anomalies. The pregnancy was terminated subsequently. At autopsy, the proband displayed a mild phenotype of hypertelorism, a small mouth, micrognathia, a narrowly arched palate, low-set ears, and clinodactyly. The brain and other organs were unremarkable. Genetic marker analysis showed a distal deletion at 21q22.3 and a breakpoint between D21S53 (present) and D21S212 (absent), centromeric to the known holoprosencephaly (HPE) minimal critical region D21S113-21qter. CONCLUSION: Genetic marker analysis helps in delineating the region of deletion in prenatally detected unbalanced cryptic translocation. Fetuses with concomitant trisomy 18p and distal 21q22.3 deletion may manifest inapparent phenotypic abnormalities in utero. Haploinsufficiency of the HPE critical region at 21q22.3 may not cause an HPE phenotype.     

Inv dup del(9p): prenatal diagnosis and molecular cytogenetic characterization by fluorescence in situ hybridization and array comparative genomic hybridization

ObjectiveTo present molecular cytogenetic characterization of prenatally detected inverted duplication and deletion of 9p, or inv dup del(9p).Materials, Methods, and ResultsA 35-year-old primigravid woman underwent amniocentesis at 16 weeks of gestation because of advanced maternal age. Amniocentesis revealed a derivative chromosome 9, or der(9) with additional material at the end of the short arm of one chromosome 9. Parental karyotypes were normal. Level II ultrasound showed ventriculomegaly and normal male external genitalia. Repeated amniocentesis was performed at 20 weeks of gestation. Array comparative genomic hybridization revealed a 0.70-Mb deletion at 9p24.3 and an 18.36-Mb duplication from 9p24.3 to 9p22.1. The distal 9p deletion encompassed the genes of DOCK8, ANKRD15, FOXD4, DMRT1, and DMRT3. Fluorescence in situ hybridization analysis using bacterial artificial chromosome clone probes specific for 9p confirmed that the der(9) was derived from the inv dup del(9p). The karyotype of the fetus was 46,XY,inv dup del(9)(:p22.1→p24.3::p24.3→qter)dn or 46,XY,der(9) del(9)(p24.3) inv dup(9)(p22.1p24.3)dn. Polymorphic DNA marker analysis determined a maternal origin of the inv dup del(9p). A 512-g male fetus was subsequently terminated at 22 weeks of gestation with facial dysmorphism. The fetus had normal male external genitalia without sex reversal.ConclusionFluorescence in situ hybridization and array comparative genomic hybridization are useful to determine the nature of a prenatally detected aberrant chromosome derived from the inv dup del. Male fetuses with inv dup del(9p) and haploinsufficiency of DMRT1 and DMRT3 may present normal male external genitalia without sex reversal.     

Prenatal diagnosis of holoprosencephaly (HPE) in a fetus with a recombinant (18)dup(18q)inv(18)(p11.31q11.2)mat

Alobar holoprosencephaly (HPE) was identified by ultrasonography at 18 weeks' gestation in a fetus of a 29-year-old G2P0A1 woman. HPE has been described in association with various chromosomal anomalies. Amniocentesis was performed and a rearrangement of chromosome 18 resembling an isochromosome for the long arm of chromosome 18 was found. Subsequently, the mother was found to have a pericentric inversion of chromosome 18 with breakpoints at p11.31 and q11.2. The karyotype of the fetus was re-interpreted as 46,XX, rec(18)dup(18q)inv(18)(p11.31q11.2)mat. This is the first case of a parental inversion leading to a deficiency of 18p11.31 to 18pter associated with HPE.     

Prenatal diagnosis and molecular cytogenetic analysis of partial monosomy 10q (10q25.3-->qter) and partial trisomy 18q (18q23-->qter) in a fetus associated with cystic hygroma and ambiguous genitalia

OBJECTIVES: To present the prenatal diagnosis and molecular cytogenetic analysis of a fetus with nuchal cystic hygroma and ambiguous genitalia. CASE AND METHODS: Amniocentesis was performed at 16 weeks' gestation because of the abnormal fetal sonographic finding of a large septated nuchal cystic hygroma. Genetic amniocentesis revealed a terminal deletion in the long arm of chromosome 10. The paternal karyotype was subsequently found to be 46,XY,t(10;18)(q25.3;q23). The maternal karyotype was normal. The pregnancy was terminated. A hydropic fetus was delivered with a septated nuchal cystic hygroma and ambiguous genitalia. Fluorescence in situ hybridization (FISH), microarray-based comparative genomic hybridization (CGH), and polymorphic DNA markers were used to investigate the involved chromosomal segments. RESULTS: FISH study showed absence of the 10q telomeric probe and presence of the 18q telomeric probe in the derivative chromosome 10. Microarray-based CGH analysis showed loss of distal 10q and gain of distal 18q. Polymorphic DNA marker analysis determined the breakpoints. The fetal karyotype was 46,XY,der(10)t(10;18)(q25.3;q23)pat. The chromosome aberration resulted in partial monosomy 10q (10q25.3-->qter) and partial trisomy 18q (18q23-->qter). CONCLUSIONS: The present case provides evidence that partial monosomy 10q (10q25.3-->qter) with partial trisomy 18q (18q23-->qter) can be a genetic cause of fetal cystic hygroma and ambiguous genitalia. Cytogenetic analysis for prenatally detected structural abnormalities may detect unexpected inherited chromosome aberrations.     

Prenatal diagnosis and molecular cytogenetic characterization of a pure ring chromosome 21 with a 4.657-Mb 21q22.3 deletion

ObjectiveWe present diagnosis and molecular cytogenetic characterization of a pure ring chromosome [r(21)] with a 4.657-Mb 21q22.3 deletion.Case reportA 44-year-old woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype 46,XX,r(21)(p11.2q22.3). Prenatal ultrasound findings were unremarkable. Simultaneous array comparative genomic hybridization (aCGH) analysis on uncultured amniocytes revealed a 4.657-Mb deletion at 21q22.3. The parental karyotypes were normal. The pregnancy was subsequently terminated, and a malformed fetus was delivered with facial dysmorphism and clinodactyly. Postnatal cytogenetic analysis of umbilical cord revealed a karyotype of 46,XX,r(21)(p11.2q22.3). aCGH analysis of umbilical cord revealed the result of arr 21q22.3 (43,427,188–48,084,156) × 1.0 with a 4.657-Mb 21q22.3 deletion encompassing 57 Online Mendelian Inheritance in Man (OMIM) genes including TRPM2, TSPEAR, COL18A1, COL6A1, COL6A2, LSS, PCNT, DIP2A, S100B and PRMT2. Metaphase fluorescence in situ hybridization (FISH) analysis of the umbilical cord fibroblasts confirmed a 21q22.3 deletion.ConclusionPrenatal diagnosis of an r(21) should include molecular cytogenetic characterization such as aCGH and FISH to determine the extent of the 21q22.3 deletion.     

Prenatal diagnosis of partial monosomy 18p(18p11.2-->pter) and trisomy 21q(21q22.3-->qter) with alobar holoprosencephaly and premaxillary agenesis

A prenatal diagnosis of partial monosomy 18p(18p11.2-->pter) and trisomy 21q(21q22.3-->qter) in a fetus with alobar holoprosencephaly (HPE) and premaxillary agenesis (PMA) but without the classical Down syndrome phenotype is reported. A 27-year-old primigravida woman was referred for genetic counselling at 21 weeks' gestation due to sonographic findings of craniofacial abnormalities. Level II ultrasonograms manifested alobar HPE and median orofacial cleft. Cytogenetic analysis and fluorescence in situ hybridization (FISH) on cells obtained from amniocentesis revealed partial monosomy 18p and a cryptic duplication of 21q,46,XY,der(18)t(18;21)(p11.2;q22.3), resulting from a maternal t(18;21) reciprocal translocation. The breakpoints were ascertained by molecular genetic analysis. The pregnancy was terminated. Autopsy showed alobar HPE with PMA, pituitary dysplasia, clinodactyly and classical 18p deletion phenotype but without the presence of major typical phenotypic features of Down syndrome. The phenotype of this antenatally diagnosed case is compared with those observed in six previously reported cases with monosomy 18p due to 18;21 translocation. The present study is the first report of concomitant deletion of HPE critical region of chromosome 18p11.3 and cryptic duplication of a small segment of distal chromosome 21q22.3 outside Down syndrome critical region. The present study shows that cytogenetic analyses are important in detecting chromosomal aberrations in pregnancies with prenatally detected craniofacial abnormalities, and adjunctive molecular investigations are useful in elucidating the genetic pathogenesis of dysmorphism.     

Prenatal diagnosis and molecular cytogenetic characterization of an interstitial deletion of 18q12.1-q12.3 encompassing DTNA,CELF4 and SETBP1

Objective

We present prenatal diagnosis and molecular cytogenetic characterization of an interstitial deletion of 18q12.1-q12.3.

Interstitial deletion del(10)(q25.2q25.3 approximately 26.11)--case report and review of the literature

OBJECTIVES: To present the clinical, cytogenetic, and molecular cytogenetic findings of prenatally diagnosed interstitial deletion 10q25.2-q26.1. The majority of distal 10q deletions are pure terminal deletions with breakpoints in 10q25 and 10q26. Only four patients have been described so far with interstitial deletions involving bands 10q25.2-q26.1. METHODS: Postmortem physical examination and autopsy of the foetus after medically terminated pregnancy. GTG-banding, reverse painting, and FISH analysis with BAC clones on amniocyte metaphases were performed to determine the extent of the deletion. RESULTS: At 20 weeks the eutrophic female foetus showed pronounced microretrogeny and hypertelorism, clubfeet as well as minor internal anomalies like pancreas anulare, atypically lobed liver, and missing choleocystis. Cardiac anomalies were not observed and the genitalia were of a normal female. The deletion encompasses 6-Mb and is associated with hemizygosity for 30 genes, including the genes for beta-tectorin, the beta-1 adrenergic receptor, and the alpha-2A adrenergic receptor. CONCLUSION: An interstitial deletion del(10)(q25.2q25.3 approximately 26.11) was confirmed by FISH with mapped BAC clones. Clinical and molecular cytogenetic analyses of further interstitial 10q deletions are necessary to assess whether the phenotypic manifestations differ between deletions that are interstitial compared to those that include also the terminal region of chromosome 10.     

Prenatal diagnosis of a distal 3p deletion associated with fetoplacental chromosomal discrepancy and confined placental mosaicism detected by array comparative genomic hybridization

ObjectiveThis study is aimed at prenatal diagnosis of a distal 3p deletion associated with fetoplacental chromosomal discrepancy and confined placental mosaicism, and providing evidence for the limitation of array comparative genomic hybridization (aCGH) on placental tissues for molecular cytogenetic characterization of prenatally detected aneuploidy.Case ReportA 30-year-old woman underwent amniocentesis at 18 weeks of gestation because of maternal anxiety. Results of amniocentesis revealed a distal deletion of chromosome 3p. A malformed female fetus was delivered at 20 weeks of gestation with brachycephaly and facial dysmorphisms, and a cytogenetic analysis of the cord blood revealed a karyotype of 46,XX,del(3)(p26.1),inv(9)(p12q13). A whole-genome aCGH on uncultured cord blood and placental tissue was performed. The aCGH on cord blood revealed a 7.4-Mb deletion at 3p26.3-p26.1. However, the aCGH on placental tissue revealed a 32.42-Mb gene dosage increase at 3p26.1-p22.1 and a 26.28-Mb gene dosage increase at 1p36.33-p36.11 in addition to a 7.4-Mb deletion at 3p26.3-p26.1, indicating confined placental mosaicism for partial trisomy 3p (3p26.1→p22.1) and mosaicism for partial trisomy 1p (1p36.33→p36.11). The 7.4-Mb deleted region of 3p26.3-p26.1 contained the following genes: CHL1, CNTN4, CRBN, LRRN1, and ITPR1.ConclusionFetal tissue and amniocytes offer more reliable resources for aCGH characterization of prenatally detected aneuploidy compared with placental tissues. A molecular cytogenetic evaluation of prenatally detected aneuploidy using placental tissue should raise concerns of confined placental mosaicism and fetoplacental chromosomal discrepancy.     

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

ObjectiveWe 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 reportA 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.ConclusionA 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.     

Cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes in mosaic 46,XX,dup(9)(q22.3q34.1)/46,XX at amniocentesis in a pregnancy with a favorable outcome

ObjectiveWe present our observation of cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes in mosaic dup(9)(q22.3q34.1) at amniocentesis in a pregnancy with a favorable outcome.Case reportA 37-year-old, gravida 4, para 0, woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 46,XX, dup(9)(q22.3q34.1)[8]/46,XX[16]. Prenatal ultrasound findings were unremarkable. She was referred for genetic counseling, and repeat amniocentesis was performed at 21 weeks of gestation, which revealed a karyotype of 46,XX,dup(9)(q22.3q34.1)[7]/46,XX[25]. Simultaneous array comparative genomic hybridization (aCGH) on the DNA extracted from uncultured amniocytes revealed no genomic imbalance, or arr (1–22,X) × 2. Interphase fluorescence in situ hybridization (FISH) analysis on 105 uncultured amniocytes detected only one cell with the dup 9q signal with a mosaic dup 9q level of 1%, compared with 0% in normal control. At 37 weeks of gestation, a 2640-g female baby was delivered with no phenotypic abnormality. The cord blood had a karyotype of 46,XX,dup(9) (q22.3q34.1)[4]/46,XX[36], the umbilical cord had a karyotype of 46,XX,dup(9) (q22.3q34.1)[2]/46,XX[38], and the placenta had a karyotype of 46,XX. aCGH analysis on cord blood revealed no genomic imbalance. At age 2½ months, the baby was doing well, the peripheral blood of the baby had a karyotype of 46,XX,dup(9) (q22.3q34.1)[4]/46,XX[36], and interphase FISH analysis on buccal mucosal cells revealed no dup 9q signal in 100 buccal mucosal cells.ConclusionCytogenetic discrepancy may occur between cultured amniocytes and uncultured amniocytes in mosaic dup(9) (q22.3q34.1). Molecular cytogenetic analysis on uncultured amniocytes is useful for rapid distinguishing pseudomosaicism from true mosaicism under such a circumstance.     

Inv dup del(10q): identification by fluorescence in situ hybridization and array comparative genomic hybridization in a fetus with two concurrent chromosomal rearrangements

ObjectiveTo present molecular cytogenetic characterization of an inverted duplication with terminal deletion of 10q, or inv dup del(10q) in a fetus with two concurrent chromosomal rearrangements.Materials, Methods and ResultsA 39-year-old woman underwent amniocentesis at 20 weeks of gestation because of advanced maternal age. Amniocentesis revealed a der(10) with additional material at the end of the long arm of chromosome 10, a der(9) and a der(22). Parental karyotypes were normal. A de novo unbalanced complex chromosomal rearrangement (CCR) was diagnosed by conventional cytogenetics, but the breakpoints could not be defined. The pregnancy was subsequently terminated, and a malformed fetus was delivered with facial dysmorphism. Postnatal analysis of fetal tissues using spectral karyotyping, fluorescence in situ hybridization, multicolor banding, and array-comparative genomic hybridization identified an inv dup del(10q) with an inverted duplication of 10q25.1→q26.2 and a terminal deletion of 10q26.2→qter, and a balanced reciprocal translocation between chromosomes 9 and 22. Microsatellite analysis determined a paternal origin of the inv dup del(10q). The karyotype of the fetus was 46,XX,t(9;22)(p23;q13),der(10)del(10)(q26.2) dup(10)(q26.2q25.1)dn.ConclusionA de novo inv dup del(10q) can be associated with a concurrent de novo balanced reciprocal translocation and should be differentiated from an unbalanced CCR by molecular cytogenetic techniques.     

Chromosome 15q overgrowth syndrome: prenatal diagnosis, molecular cytogenetic characterization, and perinatal findings in a fetus with dup(15)(q26.2q26.3)

ObjectiveTo present molecular cytogenetic characterization of a prenatally detected duplication of 15q26.2 → q26.3 in a fetus with overgrowth.Case ReportA 34-year-old para 0 woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age. Amniocentesis revealed a derivative chromosome 15, or der(15), with additional material at the end of the long arm of one chromosome 15. Parental karyotypes were normal. Fetal overgrowth was first noted at 21 weeks of gestation. Repeated amniocentesis was performed at 22 weeks of gestation. Array comparative genomic hybridization revealed a 4.71-Mb duplication from 15q26.2 to 15q26.3 encompassing the IGF1R gene. Fluorescence in situ hybridization analysis using the bacterial artificial chromosome clone probes specific for 15q26.2-q26.3 and the subtelomeric region of 15q showed a direct duplication and no terminal deletion in the der(15). Polymorphic DNA marker analysis determined a paternal origin of the duplication of 15q. Level II ultrasound at 23 weeks of gestation revealed a fetal biometry equivalent to 26 weeks. The pregnancy was subsequently terminated, and a 1062-g (>99^th centile) malformed fetus was delivered at 24 weeks of gestation with craniofacial dysmorphism, craniosynostosis, and overgrowth.ConclusionThe present case provides evidence for prenatal overgrowth, craniosynostosis, and characteristic facial dysmorphism in association with a duplication of 15q26.2 → q26.3 and a duplication of the IGF1R gene. Prenatal diagnosis of fetal overgrowth should include a differential diagnosis of the chromosome 15q overgrowth syndrome.     

Mosaicism for Robertsonian jumping translocation at amniocentesis: 45,XY,der(15;22)(q10;q10)mat/46,XY,i(15)(q10)/46,XY,genetic counseling,prenatal diagnosis and postnatal follow-up in a pregnancy with a favorable fetal outcome

ObjectiveWe present genetic counseling, prenatal diagnosis and postnatal follow-up of 45,XY,der(15;22)(q10;q10)mat/46,XY,i(15)(q10)/46,XY at amniocentesis in a pregnancy with a favorable fetal outcome.Case reportA 27-year-old, primigravid woman underwent amniocentesis at 19 weeks of gestation because increased nuchal translucency thickness, and the result was 45,XY,der(15;22)(q10;q10)[29]/46,XY,i(15)(q10)[3]/46,XY[5]. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed arr (1–22) × 2, (X,Y) × 1. The maternal karyotype was 45,XX,der(15;22)(q10;q10), and the paternal karyotype was 46,XY. She was referred for genetic counseling, and repeat amniocentesis performed at 23 weeks of gestation revealed 45,XY,der(15;22)(q10;q10)mat[23]/45,XY,-22[2]. aCGH analysis on uncultured amniocytes detected no genomic imbalance, and polymorphic DNA marker analysis excluded uniparental disomy (UPD) 15. Fluorescence in situ hybridization (FISH) analysis using the chromosome 15q specific probe and the chromosome 22q specific probe detected three 15q signals in 4/104 cells (3.8%). The woman was advised to continue the pregnancy, and, a 3186-g phenotypically normal male baby was delivered at 38 weeks of gestation. The umbilical cord had a karyotype of 45,XY,der(15;22)(q10;q10) (40/40 cells). When follow-up at age seven months, the neonate was normal in development, the peripheral blood had a karyotype of 45,XY,der(15;22)(q10;q10) (40/40 cells), and the buccal mucosal cells had normal signals in all 100 cells.ConclusionsMosaicism for Robertsonian jumping translocations at amniocentesis can be a transient condition and can be associated with a familial Robertsonian translocation and a favorable fetal outcome. Prenatal diagnosis of a Robertsonian jumping translocation involving chromosome 15 should include UPD 15 testing to exclude UPD 15.     

Prenatal diagnosis of concomitant distal 5q duplication and terminal 10q deletion in a fetus with intrauterine growth restriction,congenital diaphragmatic hernia and congenital heart defects

ObjectiveWe present prenatal diagnosis of concomitant distal 5q duplication and terminal 10q deletion in a fetus with intrauterine growth restriction (IUGR), congenital diaphragmatic hernia (CDH) and congenital heart defects (CHD).Case reportA 34-year-old, gravida 4, para 2, woman was referred for amniocentesis at 21 weeks of gestation because of advanced maternal age and IUGR. There was no congenital malformation in the family. Amniocentesis revealed a derivative chromosome 10 with an additional maternal on the terminal region of 10q. Array comparative genomic hybridization (aCGH) analysis on the DNA extracted from the cultured amniocytes revealed a result of arr 5q31.3q35.5 (142, 548, 354–180,696,806) × 3.0, arr 10q26.3 (132, 932, 808–135,434,178) × 1.0 [GRCh37 (hg19)] with a 2.50-Mb deletion of 10q26.3 encompassing 19 [Online Mendelian Inheritance in Man (OMIM)] genes and a 38.15-Mb duplication of 5q31.3-q35.5 encompassing 195 OMIM genes including four CDH candidate genes of NDST1, ADAM19, NSD1 and MAML1. The mother was found to have a karyotype of 46,XX,t(5; 10) (q31.3; q26.3). Therefore, the fetal karyotype was 46,XX,der(10)t(5; 10)(q31.3; q26.3)mat. Prenatal ultrasound showed IUGR, right CDH, transposition of great artery, double outlet of right ventricle and right atrial isomerism. The pregnancy was terminated, and a malformed fetus was delivered with facial dysmorphism.ConclusionFetuses with concomitant distal 5q duplication and terminal 10q deletion may present IUGR, CDH and CHD on prenatal ultrasound.