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.     

Perinatal findings and molecular cytogenetic analysis of de novo partial trisomy 16q (16q22.1-->qter) and partial monosomy 20q (20q13.3-->qter)

OBJECTIVES: To present the perinatal findings and molecular cytogenetic analysis of de novo partial trisomy 16q and partial monosomy 20q and a review of the literature. CASE AND METHODS: Obstetric ultrasound at 33 weeks' gestation revealed intrauterine growth restriction (IUGR) and dolichocephaly in a 27-year-old primigravid woman. Prenatal cytogenetic diagnosis was not offered because of the late stage of gestation. A 2800-g male baby was delivered at 41 weeks' gestation by cesarean section because of fetal distress. The infant postnatally presented characteristic craniofacial dysmorphism, hypotonia, cleft palate, congenital heart defects, a subependymal cyst, and hypospadia. Cytogenetic analysis revealed an additional material attached to the terminal region of chromosome 20q. The parental karyotypes were normal. Spectral karyotyping (SKY), fluorescence in situ hybridization (FISH), and polymorphic DNA markers were used to investigate the origin of the de novo aberrant chromosome. RESULTS: SKY using 24-color probes, FISH using specific 16p, 16q, 20 centromeric, and 20q telomeric probes, and polymorphic DNA marker analysis confirmed maternal origin of the duplication of distal 16q and the deletion of terminal 20q. Karyotype of the proband was designated as 46,XY.ish der(20)t(16;20)(q22.1;q13.3)(SKY+,16qTEL+,20qTEL-). CONCLUSIONS: Partial trisomy 16q (16q22.1-->qter) and partial monosomy 20q (20q13.3-->qter) may be associated with the perinatal findings of IUGR, dolichocephaly, hypotonia, cleft palate, congenital heart defects, a subependymal cyst, and hypospadia. SKY, FISH, and genetic marker studies help in delineating the parental origin and the regions of the deletion and duplication in the de novo unbalanced translocation.     

Prenatal diagnosis and molecular cytogenetic characterization of a derivative chromosome der(18;18)(q10;q10)del(18)(q11.1q12.1)del(18)(q22.1q22.3) presenting as apparent isochromosome 18q in a fetus with holoprosencephaly

ObjectiveTo present prenatal diagnosis and molecular cytogenetic characterization of a derivative chromosome der(18;18)(q10;q10)del(18)(q11.1q12.1)del(18)(q22.1q22.3).Materials, Methods, and ResultsA 32-year-old woman was referred for genetic counseling of prenatally detected isochromosome 18q [i(18q)]. She had undergone amniocentesis at 19 gestational weeks because of a trisomy 18 risk of 1/39 derived from abnormally low levels of maternal serum unconjugated estriol, inhibin A, α-fetoprotein, and total β-human chorionic gonadotropin. Amniocentesis revealed a karyotype of 46,XX,i(18)(q10). Parental karyotypes were normal. Prenatal ultrasound showed alobar holoprosencephaly. Repeated amniocentesis was requested and performed at 21 gestational weeks. Array-comparative genomic hybridization analyses revealed a 14-Mb deletion of 18p11.32-p11.21, a 37.8-Mb duplication of 18q12.1-q22.1, and a 6.9-Mb duplication of 18q22.3-q23. Metaphase fluorescence in situ hybridization study showed the absence of an 18q12.1-specific probe signal in one arm and the absence of an 18q22.2-specific probe signal in the other arm of the derivative chromosome. Quantitative fluorescent polymerase chain reaction analysis determined a paternal origin of the derivative chromosome. The cytogenetic result was 46,XX,der(18;18)(q10;q10)del(18)(q11.1q12.1)del(18)(q22.1q22.3). The fetus postnatally manifested cebocephaly.ConclusionConcomitant monosomy 18p and trisomy 18q can be associated with holoprosencephaly and abnormal maternal serum screening results. Array-comparative genomic hybridization, fluorescence in situ hybridization, and quantitative fluorescent polymerase chain reaction are useful in genetic counseling of prenatally detected isochromosomes by providing information on the origin and genetic components of the isochromosome.     

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.     

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 and molecular cytogenetic characterisation of a small de novo interstitial duplication 16q11.2-q13

We describe the first prenatally detected case of a small de novo interstitial duplication of chromosome 16q. This chromosomal aberration is extremely rare. Amniocentesis was indicated by advanced maternal age only. Ultrasound examinations of the foetus showed no abnormalities. Conventional and molecular cytogenetic analyses on cultured amniocytes by comparative genomic hybridisation (CGH) and fluorescence in situ hybridisation (FISH) using partial chromosome paints and a locus-specific YAC clone revealed a de novo direct duplication of the chromosomal region 16q11.2-q13 leading to a partial trisomy 16q (46,XX,dup(16)(q11.2q13)). There are only five postnatal reports of comparable duplications involving this chromosomal region. These patients presented with little or no associated dysmorphic features but with significant neurodevelopmental delay and severe behavioural problems. After genetic counselling, the parents opted for termination of pregnancy. Post-mortem examination showed slight facial dysmorphic signs, minor dysgenesis of the ovaries and an atypical outflow of the arteria thyroidea ima.     

Perinatal findings and molecular cytogenetic analyses of de novo interstitial deletion of 9q (9q22.3-->q31.3) associated with Gorlin syndrome

OBJECTIVES: To present the perinatal findings and the molecular cytogenetic analyses of a de novo interstitial deletion of 9q (9q22.3-->q31.3) associated with Gorlin syndrome. METHODS: Amniocentesis was performed at 18 weeks' gestation on a 27-year-old woman at a community hospital because of a high Down syndrome risk of 1/178, a low maternal serum alpha-fetoprotein (MSAFP) level of 0.66 multiples of the median (MoM), and a high maternal serum human chorionic gonadotrophin (MShCG) level of 3.13 MoM. The karyotype was initially determined to be 46,XY. However, fetal macrocephaly and overgrowth were found at 30 weeks' gestation. Postnatally, the infant manifested characteristic features of Gorlin syndrome. High-resolution chromosomal bandings of the peripheral blood lymphocytes, polymorphic DNA marker analysis to determine the parental origin of the deletion, array comparative genomic hybridization (CGH) to determine the extent of the chromosomal deletion, and fluorescence in situ hybridization (FISH) to determine the deletion of the PTCH gene were performed. RESULTS: The 850-band level of resolution showed an interstitial deletion of 9q (9q22.3-->q31.3). The parental karyotypes were normal. The karyotype of the proband was 46,XY,del(9)(q22.3q31.3)de novo. Polymorphic DNA marker analysis revealed that the deletion was of paternal origin. Array CGH revealed that the deleted region was about 12 Mb, encompassing the segment from 9q22.32 to 9q31.3. FISH analysis using the BAC probe RP11-34D4 and the probe RP11-43505 indicated the deletion of the PTCH gene. CONCLUSIONS: Fetuses with an interstitial deletion of 9q (9q22.3-->q31.3) may be associated with a low level of MSAFP and a high level of MShCG in the second trimester, and sonographic findings of overgrowth and macrocephaly in the third trimester.     

Prenatal diagnosis of del(15)(q26.1) and del(18)(q21.3) due to an unbalanced de novo translocation: ultrasound, molecular cytogenetic and autopsy findings

A case of partial deletion of the distal parts of chromosomes 15 and 18 [(15)(q26.1)(18)(q21.3)] due to a de novo translocation is reported. Cordocentesis and fetal karyotyping was done because of severe oligohydramnios and bilateral absence of kidneys. Renal defects are a frequent finding in fetuses with different chromosomal anomalies; this particular chromosomal rearrangement however has not been reported yet in a fetus with bilateral renal agenesis. FISH was performed for detailed clarification of the chromosomal anomaly. Prenatal karyotyping appears to be important in fetuses with renal agenesis.     

Molecular characterisation of a prenatally diagnosed 5q15q21.3 deletion and review of the literature

BACKGROUND: Ultrasound examination performed on a 32-year old woman at 30 weeks' gestation showed the presence of fetal malformations. Amniocentesis was performed. METHODS AND RESULTS: Cytogenetic analysis of cultured amniocytes revealed an interstitial deletion of the long arm of chromosome 5. Molecular studies confirmed that the deletion included the 5q15-21.3 region and was 14 Mb in size. Therefore, the karyotype was: 46,XY,del(5)(q15q21.3). In addition, analysis of polymorphic DNA markers showed that the deletion was of paternal origin. CONCLUSIONS: The pregnancy was terminated at 34 weeks' gestation. At autopsy, the fetus displayed dysmorphic features, thin limbs and renal abnormalities. The clinical findings observed in the fetus as well as in 20 cases reported previously allowed us to further delineate the phenotype of such interstitial 5q15q21.3 deletions.     

A patient with a de novo t (6;9) and an interstitial duplication of (9)(q21.2q22.1).

We report on a 4-year-old child with psychomotor retardation, general hypotonia and only mild dysmorphic features. Her chromosome constitution was 46,XX, t (6;9) (q27;q22.1), dup (9) (q21.2q22.1). This de novo interstitial duplication was confirmed using fluorescence in situ hybridisation (FISH) with band-specific probes. This is the second report of a patient with an interstitial duplication of this region of the long arm of chromosome 9. It is concluded that in a child with an abnormal phenotype and a de novo (apparently) balanced translocation, the possibility of a small duplication or deletion should be considered.     

Prenatal diagnosis of de novo terminal deletion of chromosome 7q

OBJECTIVES: To present the prenatal diagnosis and perinatal findings of a de novo terminal deletion of chromosome 7q. CASE: Amniocentesis was performed at 21-weeks gestation owing to a positive result of maternal serum multiple-marker screening. The 30-year-old woman, gravida 2, para 1, had a maternal serum multiple-marker screening test at 18-weeks gestation. The risk of Down syndrome was 1/11 calculated from the gestational age, maternal age, a maternal serum alpha-fetoprotein level of 1.026 multiples of the median (MOM), and a maternal serum free beta-human chorionic gonadotrophin (hCG) level of 8.678 MoM. Cytogenetic analysis of the cultured amniotic fluid cells revealed a de novo terminal deletion of 7q, 46,XX,del(7)(q35). Ultrasonography showed intrauterine growth restriction, microcephaly, and tetralogy of Fallot. The pregnancy was terminated subsequently. Grossly, the placenta was normal. On autopsy, the proband additionally manifested a prominent forehead, hypertelorism, epicanthus, upslanting palpebral fissures, a flat and broad nasal bridge, micrognathia, large low-set ears, overriding toes, and a normal brain. Radiography demonstrated a normal spine. Fluorescence in situ hybridization analysis demonstrated a 7q terminal deletion. Genetic marker analysis showed a maternally derived terminal deletion of chromosome 7(q35-qter). CONCLUSION: Fetuses with a de novo 7q terminal deletion may be associated with a markedly elevated maternal serum hCG level and abnormal sonographic findings of intrauterine growth restriction, microcephaly, and congenital heart defects in the second trimester.     

Prenatal diagnosis of the distal 11q deletion and review of the literature

OBJECTIVES: To present the prenatal diagnosis of de novo distal 11q deletions and a review of the literature. CLINICAL SUBJECTS AND METHODS: A 31-year-old primigravid woman underwent amniocentesis at 20 weeks' gestation because of a maternal serum alpha-fetoprotein (MSAFP) level of 2.63 multiples of the median. Amniocentesis demonstrated a karyotype of 46,XY,del(11)(q24.2). The parental karyotypes were normal. Level II ultrasound revealed short femurs and humeri, and overlapping of the toes. Postnatally, the proband manifested additional findings of the characteristic facial dysmorphism and camptodactyly. A 38-year-old gravida 2, para 1, woman underwent amniocentesis at 18 weeks' gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 46,XX,del(11)(q24.1). The parental karyotypes were normal. Level II ultrasound did not show fetal structural abnormalities. Postnatally, the proband manifested characteristic facial dysmorphism and camptodactyly. RESULTS: Of these two cases, genetic marker analysis determined the paternally derived distal deletions of chromosome 11q and the deletion breakpoints. A comparison of the present cases with the reported cases of prenatally diagnosed distal 11q deletion is made. CONCLUSION: The distal 11q deletion can be identified prenatally because of parental balanced translocations involving chromosome 11, previous-term infants with an unbalanced rearrangement, advanced parental age, sonographically detected fetal abnormalities and abnormal maternal serum screening. Fetuses with de novo distal 11q deletions may be associated with elevated MSAFP and abnormal sonographic findings of the digits and limbs in the second trimester.     

Prenatal diagnosis and molecular cytogenetic characterization of a de novo 3.19-Mb chromosome 14q32.13-q32.2 deletion of paternal origin

ObjectiveWe present prenatal diagnosis and molecular cytogenetic characterization of a de novo 3.19-Mb chromosome 14q32.13-q32.2 deletion of paternal origin.Case reportA 36-year-old woman underwent amniocentesis at 20 weeks of gestation because of an advanced maternal age. Her husband was 36 years old. Amniocentesis revealed a karyotype of 46,XY,del(14)(q32.1q32.2). Simultaneous array comparative genomic hybridization (aCGH) analysis showed the result of a 14q32.13-q32.2 deletion. Prenatal ultrasound was unremarkable. The parental karyotypes were normal and did not have such a deletion. The pregnancy was subsequently terminated, and a malformed fetus was delivered with facial dysmorphism. aCGH was applied on the DNA extracted from cord blood. Polymorphic DNA marker analysis was applied on the DNAs extracted from placenta and parental bloods. aCGH confirmed a 3.19-Mb 14q32.13-q32.2 deletion or arr 14q32.13q32.2 (96,151,751–99,341,476) × 1.0 [GRCh37 (hg19)] encompassing 10 Online Mendelian Inheritance in Man (OMIM) genes of TCL1B, TCL1A, TUNAR, BDKRB2, BDKRB1, ATG2B, GSKIP, AK7, PAPOLA and VRK1. Polymorphic DNA marker analysis confirmed a paternal origin of a de novo interstitial distal 14q deletion.ConclusionDetermination of the paternal origin of a prenatally detected de novo interstitial distal 14q deletion by polymorphic DNA marker analysis in this case is significant, and the information acquired is useful for genetic counseling, especially when amniocentesis is performed because of an advanced maternal age.     

Prenatal diagnosis of de novo proximal interstitial deletion of 9q and review of the literature of uncommon aneuploidies associated with increased nuchal translucency

OBJECTIVES: To present the prenatal diagnosis and molecular cytogenetic analysis of de novo proximal interstitial deletion of 9q and to review the literature of uncommon aneuploidies associated with increased nuchal translucency (NT). CASE: Obstetric ultrasound at 11 weeks' gestation revealed an increased NT thickness of 6.6 mm in a 31-year-old primigravid woman. At 13 weeks' gestation, repeat ultrasound examinations revealed a normal NT thickness of 1.8 mm. The subcutaneous nuchal fluid accumulation was no longer present at the following ultrasound scans. An amniocentesis was performed at 18 weeks' gestation. RESULTS: Cytogenetic analysis revealed a karyotype of 46,XX,del(9)(q21.1q22.2). The parental karyotypes were normal. At 21 weeks' gestation, a 442-g female fetus was delivered with low-set ears, hypertelorism, and a thick nuchal fold. The parental origin of the interstitial deletion of 9q was analyzed with polymorphic DNA markers. With the microsatellite markers D9S238 (9q13), D9S889 (9q21.11), and D9S253 (9q22.2), two alleles inherited from the parents were seen in the proband, but with markers D9S1780 (9q21.31), D9S303 (9q21.32), D9S252 (9q21.33), and D9S316 (9q22.1), only one maternal allele was present. The deletion was of paternal origin. CONCLUSIONS: Fetuses with uncommon aneuploidies may manifest increased NT in the first trimester. The present case provides evidence for a correlation between increased NT and interstitial 9q deletion. Prenatal identification of increased NT should alert subtle structural chromosome aberrations and prompt high-resolution karyotyping.     

Duplication dup(1)(q32q44) detected by comparative genomic hybridization (CGH): further delineation of trisomies 1q

Partial trisomy 1q is rare and mostly the result of an abnormal segregation of parental translocation chromosomes and their homologues. Only 31 cases have been described with pure partial trisomy 1q. In the fetus presented, chromosome analysis after amniocentesis had shown an unbalanced male karyotype with an aberrant chromosome 1. A de novo terminal duplication of the long arm was suspected but could not be verified by FISH in 1994. Five years after fetal death, retrospective identification of the additional material in 1q could finally be achieved by comparative genomic hybridization (CGH) using DNA extracted from formalin-fixed and paraffin-embedded fetal tissues. A direct duplication dir dup (1)(pter-->q44::q32.1-->qter) was found. Only 6 other individuals with duplication of this segment have been described so far. Comparative delineation of a dup1q phenotype with regard to size and origin of the dup (1q) segment evidenced that large duplications as well as proximal and interstitial duplications coincide with more severe visceral malformations, severe mental retar- dation and a short life span. Terminal duplications (1q32-->qter) concur with less severe malformations and longer periods of survival, but marked mental retardation. With small terminal duplications (1q42-->qter) dysmorphisms are usually mild and intellectual performance is mostly in the normal range.     

Prenatal diagnosis and molecular cytogenetic characterization of de novo distal 5p deletion and distal 22q duplication

ObjectiveWe present prenatal diagnosis and molecular cytogenetic characterization of de novo distal 5p deletion and distal 22q duplication.Case reportA 34-year-old woman was underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a derivative chromosome 5 [der(5)] with an abnormal distal 5p segment of unknown origin. The parental karyotypes were normal. Array comparative genomic hybridization (aCGH) analysis was performed on the cultured amniocytes, and the result was arr 5p15.33p13.3 (22,149–29,760,922) × 1.0, arr 22q13.2q13.33 (42, 192, 065–51,178,264) × 3.0 [GRCh37 (hg19)] with a 29.739-Mb deletion of 5p15.33-p13.3 encompassing 55 [Online Mendelian Inheritance in Man (OMIM)] genes including TPPP, TERT, SRD5A1, SEMA5A and CTNND2, and an 8.986-Mb duplication of 22q13.2-q13.33 encompassing 82 OMIM genes including TRMU, SCO2, TYMP, CPT1B and SHANK3. The fetal karyotype was 46,XY,der(5)t(5; 22)(p13.3; q13.2)dn. The pregnancy was subsequently terminated, and a malformed fetus was delivered with facial dysmorphism. Postnatal polymorphic DNA marker analysis confirmed a maternal origin of the aberrant chromosome 5.ConclusionaCGH and polymorphic DNA marker analyses can determine the nature and parental origin of the de novo chromosome aberration, and the information acquired is useful for genetic counseling.     

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 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.