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 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.     

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.     

Sacrococcygeal teratoma in a fetus with prenatally diagnosed partial trisomy 10q (10q24.3-->qter) and partial monosomy 17p (p13.3-->pter)

OBJECTIVE: Clinical features of the distal 10q trisomy syndrome consist of mental retardation, facial dysmorphism and renal and cardiac anomalies. The presence of a sacrococcygeal teratoma (SCT) in a fetus with distal 10q trisomy has not been reported yet. METHODS: A 33-year-old, G5, P2 woman with a singleton pregnancy was referred to our clinic at 24 weeks of gestation for further evaluation of a fetal sacral exophytic mass. Detailed fetal sonographic examination together with chromosomal analysis by amniocentesis was performed. RESULTS: The scan revealed a large SCT together with a persistent right umbilical vein, cardiomegaly, bilateral mild hydronephrosis and intrauterine growth retardation. The fetal karyotype showed distal 10q trisomy (10q24.3-->qter) distal monosomy 17 (p13-->pter). The fetus died after a preterm delivery at 28 weeks of gestation. Postnatal examination confirmed the prenatal findings and added the typical facial features of this syndrome, which consisted of prominent forehead, small nose with depressed nasal bridge, micrognathia and bow-shaped mouth. CONCLUSION: This case provides further evidence of a possible association between chromosomal aberrations in SCTs.     

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.     

Molecular cytogenetic characterization of de novo concomitant proximal 21q deletion of 21q11.2q21.3 and distal Xp deletion of Xp22.33p22.2 due to an unbalanced X;21 translocation detected by amniocentesis

ObjectiveWe present molecular cytogenetic characterization of de novo concomitant proximal 21q deletion of 21q11.2q21.3 and distal Xp deletion of Xp22.33p22.2 due to an unbalanced X; 21 translocation detected by amniocentesis.Case reportA 35-year-old, primigravid woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 45,X,der(X)t(X; 21) (p22.2; q21.3),-21. Simultaneous array comparative genomic hybridization (aCGH) revealed the result of an 11.9-Mb Xp22.33p22.2 deletion encompassing HCCS, SHOX, AMELX and OFD1 and a 15.4-Mb 21q11.2q21.3 deletion encompassing NRIP1 and APP. The pregnancy was subsequently terminated, and a malformed fetus was delivered with craniofacial dysmorphism. The parental karyotypes were normal. Polymorphic DNA marker analysis by quantitative fluorescence polymerase chain reaction (QF-PCR) confirmed a paternal origin of the 21q proximal deletion. Cytogenetic analysis of cord blood confirmed the karyotype of 45,X,der(X)t(X; 21) (p22.2; q21.3),-21. aCGH analysis of the cord blood confirmed the prenatal diagnosis.ConclusionQF-PCR analysis is useful for determination of the parental origin of a de novo unbalanced X; autosome translocation detected by prenatal diagnosis. The information acquired is useful for genetic counseling under such a circumstance.     

Unbalanced cryptic translocation der(14)t(9;14)(q34.3;q32.33) identified by subtelomeric FISH

We investigated a girl with dysmorphic features and moderate developmental delay by subtelomeric FISH (fluorescence in-situ hybridization). We found an unbalanced cryptic translocation, t(9;14)(q34.3;q32.33), resulting in a subtelomeric deletion of 14q and duplication of 9q deriving from a balanced translocation in the mother. A review of the literature suggests that the phenotype of our case is related to the 14 qter deletion, without signs of concomitant partial trisomy 9. The case reinforces the value of subtelomeric screening for genetic counselling.     

Familial cryptic translocation with deletion 4q33-->4qter and duplication 7q34-->7qter in brothers with mental retardation,macrocephaly and iris coloboma

The association of moderate mental retardation, behavioural problems, macrocephaly, dysmorphic features with iris coloboma, and supernumerary nipples was observed in two brothers with a terminal deletion 4q33-->4qter and a terminal duplication 7q34-->7qter. The aberration was detected by subtelomere FISH screening and (probably) resulted from a cryptic familial translocation (4;7)(q33;q34).     

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.     

Partial monosomy 13q (13q21.32--->qter) and partial trisomy 8p (8p1--->pter) presenting with anencephaly and increased nuchal translucency: array comparative genomic hybridization characterization

ObjectiveTo present array comparative genomic hybridization (aCGH) characterization of partial monosomy 13q (13q21.32→qter) and partial trisomy 8p (8p12→pter) presenting with anencephaly and increased nuchal translucency (NT).Case ReportA 34-year-old primigravid woman was referred to the hospital at 12 weeks of gestation for termination of the pregnancy because of major structural abnormalities of the fetus. Prenatal ultrasound revealed a malformed fetus with anencephaly and an increased NT thickness of 5 mm at 12 weeks of gestation. Cytogenetic analysis of the fetus revealed a derivative chromosome 13. The mother was subsequently found to carry a balanced reciprocal translocation between 8p12 and 13q21. Bacterial artificial chromosome-based aCGH using fetal DNA demonstrated partial trisomy 8p and partial monosomy 13q [arr cgh 8p23.3p12 (RP11-1150M5→RP11-1145H12)×3, 13q21.32q34 (RP11-326B4→RP11-450H16)×1]. Oligonucleotide-based aCGH showed a 36.7-Mb duplication of distal 8p and a 48.4-Mb deletion of distal 13q. The fetal karyotype was 46,XY,der(13) t(8;13)(p12;q21.32)mat. The maternal karyotype was 46,XX,t(8;13)(p12;q21.32).ConclusionThe 13q deletion syndrome can be associated with neural tube defects and increased NT in the first trimester. Prenatal sonographic detection of neural tube defects should alert chromosomal abnormalities and prompt cytogenetic investigation, which may lead to the identification of an unexpected parental translocation involving chromosomal segments associated with neural tube development.     

Prenatal diagnosis of partial trisomy 3p (3p21-->pter) and partial monosomy 11q (11q23-->qter) associated with abnormal sonographic findings of holoprosencephaly, orofacial clefts, pyelectasis and a unilateral duplex renal system

Patients with partial trisomy 3p seldom present major dysmorphic features, and holoprosencephaly occurs in only 10% of the cases with partial trisomy 3p. It has been suggested that multiple genetic hits or environmental exposures are required for the clinical expression of holoprosencephaly. At 16 weeks of gestation, prenatal sonography identified a fetus with holoprosencephaly, orofacial clefts, pyelectasis, and a unilateral duplex renal system. Amniocentesis revealed the karyotype of 46,XX,der(11)t(3;11)(p21;q23)pat with partial trisomy 3p (3p21-->pter) and partial monosomy 11q (11q23-->qter). The pregnancy was subsequently terminated. Postnatally, the proband showed hypotelorism, a depressed nasal bridge, orofacial clefts and holoprosencephaly-premaxillary agenesis. The present case provides evidence that partial trisomy 3p/monosomy 11q can be a genetic cause of holoprosencephaly and del(11)(q23-->qter) is associated with a duplex renal system.     

Molecular cytogenetic characterization of a de novo unbalanced translocation leading to trisomy 17q25-->qter and monosomy 18p11.3-->pter in a girl with dysmorphic features

An 18-year-old, gravida 1 underwent percutaneous umbilical blood sampling (PUBS) because of positive triple screen, oligohydramnios and markedly short fetal bones. Chromosome analysis showed an abnormal chromosome 18 with unidentified chromatin at the end of the p-arm. Parental karyotypes were normal. FISH analyses with wcp18 showed additional material of unknown origin on the derivative chromosome 18. Further FISH analysis with subtelomeric probes showed normal signals for the long arm of chromosome 18 (18q23) while no signals were observed for the short arm (18p11.32). These findings were confirmed using a YAC probe from the short arm of 18. The infant was delivered at 30 weeks of gestation. At age 3 months, she was developmentally delayed and has multiple dysmorphic features. Further molecular cytogenetic studies including M-FISH and subtelomere probes showed that the additional material on chromosome 18 consisted of the distal 17q25-->qter region. Based on these studies the karyotype has been interpreted as 46,XX,der(18)t(17;18)(q25;p11.32). To the best of our knowledge, this is the first report of partial monosomy 18p and partial trisomy 17q in a patient with no major CNS malformations. This case shows the importance of molecular cytogenetic techniques in detailed characterization of de novo chromosome rearrangements.     

Semilobar holoprosencephaly prenatal diagnosis: an unexpected complex rearrangement in a de novo apparently balanced reciprocal translocation on karyotype

We report a semilobar holoprosencephaly (HPE) in a post-intracytoplasmic-sperm-injection pregnancy. It was suggested by ultrasonography (US), documented on karyotype, identified with magnetic resonance imaging (MRI), established after birth and confirmed on post-mortem autopsy. An amniocentesis revealed a de novo apparently balanced reciprocal translocation 46,XY, t(7;8) (q31.3;q12). Fluorescence in situ hybridization (FISH) identified a deletion in the region of the Sonic Hedgehog gene (SHH) on der(8); nevertheless, the subtelomeric regions for chromosomes 7 and 8 were present. The parents decided to continue the pregnancy; a boy was born and survived for 3 days. The brain autopsy confirmed the semilobar HPE previously noted on US and MRI. Further, band-specific FISH revealed, in addition to SHH deletion, the presence of an inversion in the 7q translocated material on der(8). The parents' karyotypes were normal. An unexpected complex rearrangement was present in a de novo apparently balanced reciprocal translocation in a semilobar HPE.     

Prenatal diagnosis of a fetus affected with Down syndrome and deletion 1p36 syndrome by fluorescence in situ hybridization and spectral karyotyping

OBJECTIVE: A fetus having partial trisomy of the distal part of chromosome 21q due to a de novo translocation is reported here. METHOD: A 29-year-old woman received amniocentesis at 18 weeks of gestation because of abnormal ultrasound findings including bilateral choroid plexus cysts, atrioventricular septal defects, rocker-bottom feet, and possible hydrocephalus. RESULTS: Cytogenetic analysis revealed 46,XY, add(1)(p36.3), in which an additional material of unknown origin was attached to one of the terminal short arms of chromosome 1. Parental blood studies showed normal karyotypes in both parents. Spectral karyotyping was then performed and the origin of the additional material locating at chromosome 1p was found to be from chromosome 21. Conventional fluorescence in situ hybridization analysis was also used and confirmed the spectral karyotyping findings by use of a chromosome 21 specific painting probe, a locus specific probe localized within bands 21q22.13-q22.2 and a 21q subtelomeric probe. A hidden Down syndrome caused by a de novo translocation in this fetus was therefore diagnosed and the karyotype was designated as 46,XY, der(1)t(1;21)(p36.3;q22.1).ish der(1)(WCP21+, LSI 21+, 1pTEL-, 21q TEL+) de novo. Clinical features of the 1p36 deletion syndrome are also reviewed and may contribute to some features of this fetus. Termination of pregnancy was performed at 20 weeks of gestation. CONCLUSION: To our knowledge, our case appears to be the first to have partial monosomy 1p and partial trisomy 21q caused by de novo translocation being diagnosed prenatally.     

Mosaic ring chromosome 21, monosomy 21, and isodicentric ring chromosome 21: prenatal diagnosis, molecular cytogenetic characterization, and association with 2-Mb deletion of 21q21.1-q21.2 and 5-Mb deletion of 21q22.3

ObjectiveTo present the perinatal findings and molecular cytogenetic characterization of prenatally detected mosaic r(21).Materials, Methods, and ResultsA 29-year-old primigravid woman underwent amniocentesis at 22 weeks’ gestation because of hyperechogenic cardiac foci and intrauterine growth restriction. Amniocentesis revealed a karyotype of 46,XY,r(21)[15]/45,XY,–21[5]. The parental karyotypes were normal. The woman requested repeat amniocentesis. Oligonucleotide-based array comparative genomic hybridization was applied to the uncultured amniocytes, rapidly detecting a 2.09-Mb deletion of 21q21.1–q21.2 (21,495,262–23,580,815 bp) and a 5.03-Mb deletion of 21q22.3–q22.3 (41,887,412–46,914,715 bp). Cytogenetic analysis revealed a karyotype of 46,XY,r(21)[8]/45,XY,–21[3]/46,XY,idic r(21)[1]. The pregnancy was terminated, and a malformed fetus was delivered with clinodactyly, short big toes, separation between the first and second toes, prominent nasal bridge, downward slanting palpebral fissures, protuberant occiput, prominent forehead, broad anteverted nasal tip, long philtrum, thin upper lip, small mouth, and micrognathia. The placenta had a karyotype of 46,XY,r(21)[83]/45,XY,–21[11]/46,XY,idic r(21)[6], and the cord blood lymphocytes had a karyotype of 46,XY,r(21)[88]/45,XY,–21[9]/46,XY,idic r(21)[3]. Polymorphic DNA marker analysis determined a maternal origin for the deletion.ConclusionAn extra interstitial 21q deletion can be associated with mosaic r(21) in addition to a terminal 21q deletion. aCGH is useful in determining the breakpoints and associated subtle structural abnormalities in cases of prenatally detected ring chromosome in order to facilitate genetic counseling.     

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 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.     

A case of 46,X,der(X)(pter-->q21::p21-->pter) with gonadal dysgenesis, tall stature, and endometriosis

Objective: To report a case of 46,X,der(X)(pter→q21::p21→pter) with gonadal dysgenesis, tall stature, and endometriosis.

Design: Case report.

Setting: A university hospital.

Patient(s): A 20-year-old primary amenorrheal woman receiving estrogen-progestogen substitution.

Intervention(s): G-banding, comparative genomic hybridization, fluorescence in situ hybridization (FISH), and laparoscopy.

Main Outcome Measure(s): A recombinant X chromosome, 46,X,der(X)(pter→q21::p21→pter), and pelvic endometriosis.

Result(s): The patient’s chromosomal abnormality was misjudged by the use of G-banding as a distal part deletion of the long arm in one X chromosome. Comparative genomic hybridization and fluorescence in situ hybridization analyses with locus-specific probes revealed 46,X,der(X)(pter→q21::p21→pter). The laparoscopic examination showed bilateral streak gonads and blue berry spots at the pelvic peritoneum, which were confirmed by evaluation of biopsy specimens.

Conclusion(s): Recent advances of genetic strategies make it easy to determine karyotype and phenotype abnormalities. We have to keep our mind on the potential of endometriosis with patients who are receiving estrogen-progestogen substitution.     

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.