Prenatal diagnosis of familial 3p26.3p25.3 deletion in a pregnancy associated with a favorable fetal outcome and asymptomatic carrier parent and family members in three generations.

OBJECTIVE: We present prenatal diagnosis of familial 3p26.3p25.3 deletion in a pregnancy associated with a favorable fetal outcome and asymptomatic carrier parent and family members in three generations. CASE REPORT: A 35-year-old, gravida 2, para 1, woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age and the carrier of distal 3p deletion. She was phenotypically normal, and there was no family history of congenital anomalies. Amniocentesis revealed a karyotype of 46,XY,del(3)(p26.1). Repeat amniocentesis at 21 weeks of gestation revealed a karyotype of 46,XY,del(3)(p25.3). Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes showed the result of arr 3p26.3p25.3 (117,735-8,709,972) × 1.0 [GRCh37 (hg19)] with an 8.59-Mb deletion of 3p26.3p25.3 encompassing 14 OMIM genes of CHL1, CNTN6, CNTN4, IL5RA, TRNT1, CRBN, SETMAR, SUMF1, ITPR1, BHLHE40, ARL8B, GRM7, LMCD1 and SSUH2. Cytogenetic analysis of parental bloods revealed a karyotype of 46,XX,del (3) (p25.3) in the mother and 46,XY in the father. The woman's 69-year-old mother and her 2-year-old elder son carried the same aberrant chromosome of 3p25.3→p26.3 deletion by conventional cytogenetic analysis but manifested no phenotypic abnormality. aCGH analysis of the peripheral bloods showed that the woman's mother and her elder son had the same 8.59-Mb deletion of 3p26.3p25.3. The woman was advised to continue the pregnancy. At 39 weeks of gestation, a 3040-g healthy male baby was delivered. When follow-up at age 2½ years, the neonate was normal in development and showed no apparent phenotypic abnormality. CONCLUSION: Distal 3p deletion of 3p26.3p25.3 involving the OMIM genes from CHL1 to SSUH2 can be associated with no apparent phenotypic abnormality.

Low-level mosaic trisomy 21 at amniocentesis and cordocentesis in the second trimester in a pregnancy associated with positive non-invasive prenatal testing for trisomy 21, perinatal progressive decrease of the trisomy 21 cell line and a favorable fetal outcome.

OBJECTIVE: We present low-level mosaic trisomy 21 at amniocentesis and cordocentesis in a pregnancy associated with a favorable fetal outcome. CASE REPORT: A 26-year-old, primigravid woman underwent amniocentesis at 17 weeks of gestation because of positive non-invasive prenatal testing (NIPT) for trisomy 21 at 16 weeks of gestation. Amniocentesis revealed a karyotype of 47,XX,+21[3]/46,XX[17], and multiplex ligation-dependent probe amplification (MLPA) on uncultured amniocytes revealed rsa X(P095) × 2, (13, 18, 21) × 2. She underwent cordocentesis (cord blood sampling) at 21 weeks of gestation which revealed a karyotype of 47,XX,+21[2]/46,XX[48]. At 27 weeks of gestation, she was referred to our hospital for genetic counseling, and repeat amniocentesis revealed a karyotype of 46,XX in 20/20 colonies. Quantitative fluorescent polymerase chain reaction (QF-PCR) analysis on the DNA extracted from uncultured amniocytes and parental bloods excluded uniparental disomy (UPD) 21. Array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed arr (1-22,X) × 2, Y × 0 with no genomic imbalance. Interphase fluorescence in situ hybridization (FISH) analysis on 104 uncultured amniocytes detected one cell (1/104 = 0.9%) with trisomy 21, while the rest cells were disomy 21, compared with 0% (0/100) in the normal control. The woman was encouraged to continue the pregnancy. The pregnancy was carried to 38 weeks of gestation, and a 2771-g female baby was delivered no phenotypic abnormality. aCGH analysis on the cord blood showed arr (1-22,X) × 2, Y × 0 with no genomic imbalance. The umbilical cord had a karyotype of 47,XX,+21[3]/46,XX[37]. The placenta had a karyotype of 46,XX. When follow-up at age 3½ months, the neonate was phenotypically normal and had normal development. The peripheral blood had a karyotype of 46,XX in 40/40 cells. Interphase FISH analysis on buccal mucosal cells detected normal disomy 21 cells in 100/100 cells. CONCLUSION: Low-level mosaic trisomy 21 at amniocentesis and cordocentesis in the second trimester can be associated with perinatal progressive decrease of the trisomy 21 cell line and a favorable fetal outcome.

High-level mosaic trisomy 21 at amniocentesis in a pregnancy associated with positive NIPT for trisomy 21, prenatal progressive decrease of the trisomy 21 cell line, acute fatty liver of pregnancy and intrauterine fetal death in late gestation.

OBJECTIVE: We present high-level mosaic trisomy 21 at amniocentesis in a pregnancy associated with positive non-invasive prenatal testing (NIPT) for trisomy 21, prenatal progressive decrease of the trisomy 21 cell line, acute fatty liver of pregnancy and intrauterine fetal death (IUFD) in late gestation. CASE REPORT: A 32-year-old, primigravid woman underwent amniocentesis at 17 weeks of gestation because of positive NIPT for trisomy 21 at 12 weeks of gestation. This pregnancy was conceived by in vitro fertilization. She did not have obesity, diabetes mellitus, hepatic biliary disorders and preeclampsia. Amniocentesis revealed a karyotype of 47,XY,+21[10]/46,XY[11], and array comparative genomic hybridization (aCGH) analysis on uncultured amniocytes revealed the result of arr (21) × 2-3. She was referred for genetic counseling, and repeat amniocentesis performed at 21 weeks of gestation revealed the karyotype of 47,XY,+21[10]/46,XY[28]. The parental karyotypes and fetal ultrasound findings were normal. Simultaneous molecular analysis on uncultured amniocytes showed no uniparental disomy 21, but a maternal origin of trisomy 21 by quantitative fluorescent polymerase chain reaction (QF-PCR) and the result of arr 21q11.2q22.3 × 2.5 by aCGH analysis. At 27 weeks of gestation, she underwent a third amniocentesis, of which conventional cytogenetic analysis revealed the result of 47,XY,+21[5]/46,XY[17] in cultured amniocytes, and aCGH analysis revealed arr 21q11.2q22.3 × 2.48, and interphase fluorescence in situ hybridization (FISH) analysis revealed 39% (39/100 cells) mosaicism fro trisomy 21 in uncultured amniocytes. At 36 weeks of gestation, the woman suffered from a sudden onset of acute fatty liver and IUFD. A 3522-g male baby was delivered without Down syndrome phenotype. The umbilical cord had a karyotype of 47,XY,+21[10]/46,XY[30]. aCGH analysis on the skin and placenta showed arr 21q11.2q22.3 × 2.73 and arr 21q11.2q22.3 × 2.75, respectively. QF-PCR analysis of umbilical cord, placenta and skin showed a maternal origin of trisomy 21. CONCLUSION: High-level mosaic trisomy 21 at amniocentesis can be associated with prenatal progressive decrease of the trisomy 21 cell line in cultured amniocytes and perinatal fetal mortality and maternal morbidity.

45,X/46,XX at the first amniocentesis, and 45,X/47,XXX/46,XX at the repeat amniocentesis and at birth in a pregnancy associated with a favorable fetal outcome, perinatal progressive decrease of the 45,X cell line and cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes.

OBJECTIVE: We present 45,X/46,XX at the first amniocentesis, and 45,X/47,XXX/46,XX at the repeat amniocentesis and at birth in a pregnancy associated with a favorable fetal outcome, perinatal progressive decrease of the 45,X cell line and cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes. CASE REPORT: A 43-year-old, gravida 3, para 1, woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 45,X[4]/46,XX[20]. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed arr (X) × 3 [0.24], consistent with 24% mosaicism for triple X. Repeat amniocentesis at 20 weeks of gestation revealed the result of 45,X[17]/47,XXX[8]/46,XX[121]. She was referred for genetic counseling, and the third amniocentesis performed at 30 weeks of gestation revealed the result of 45,X[3]/47,XXX[2]/46,XX[16]. The mother had a karyotype of 46,XX. aCGH analysis on the DNA extracted from uncultured amniocytes showed arr Xp22.33q28 × 2.2 (log2 ratio = 0.15), consistent with 20% mosaicism for triple X. Interphase fluorescence in situ hybridization (FISH) analysis on 100 uncultured amniocytes showed that 11 cells (11%) were monosomy X, seven cells (7%) were triple X, and the others were disomy X. At 39 weeks of gestation, a 3,620-g phenotypically normal female baby was delivered without any phenotypic abnormality. The karyotypes of cord blood, umbilical cord and placenta were 47,XXX[7]/45,X[1]/46,XX[32], 47,XXX[13]/46,XX[27] and 47,XXX[2]/46,XX[38], respectively. When follow-up at age one month, the neonate was phenotypically normal, and FISH analysis on 106 buccal mucosal cells showed that eight cells (7.5%) were monosomy X, seven cells (6.6%) were triple X, and the others were disomy X. CONCLUSION: Mosaic 45,X/46,XX at amniocentesis may be in fact mosaic 45,X/47,XXX/46,XX and can be associated with a favorable fetal outcome and perinatal progressive decrease of the 45,X cell line.

Perinatal detection of disomy X cell line by fluorescence in situ hybridization in a pregnancy with 45,X/47,XXX at amniocentesis, cytogenetic discrepancy in various tissues and a favorable outcome.

OBJECTIVE: We present perinatal detection of disomy X cell line by fluorescence in situ hybridization (FISH) in a pregnancy with 45,X/47,XXX at amniocentesis, cytogenetic discrepancy in various tissues and a favorable outcome. CASE REPORT: A 34-year-old, gravida 3, para 1, woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 45,X[22]/47,XXX[10]. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed the result of arr (X) × 1-2, (1-22) × 2, consistent with 32% mosaicism for monosomy X. She was referred for genetic counseling at 19 weeks of gestation. Prenatal ultrasound findings and parental karyotypes were normal. Repeat amniocentesis at 29 weeks of gestation revealed a karyotype of 45,X[36]/47,XXX[4] (Fig. 1) in cultured amniocytes. Simultaneous molecular analysis on uncultured amniocytes revealed the result of arr (1-22) × 2, Y × 0 by aCGH with no genomic imbalance, and 15% (15/100 cells) mosaicism for disomy X, 61% (61/100 cells) mosaicism for monosomy X and 24% (24/100 cells) mosaicism for triple X by interphase fluorescence in situ hybridization (FISH) analysis. The pregnancy was encouraged to continue and at 37 weeks of gestation, a 2834-g phenotypically normal female baby was delivered. The karyotypes of cord blood, umbilical cord and placenta were 45,X[33]/47,XXX[7], 45,X[30]/47,XXX[10] and 47,XXX[38]/45,X[2], respectively. When follow-up at age three months, the neonate was normal in development. FISH analysis on 99 buccal mucosal cells showed 49% (48/99 cells) mosaicism for monosomy X, 8% (8/99 cells) mosaicism for triple X and 43% (42/99 cells) mosaicism for disomy X (Fig. 2). Peripheral blood had a karyotype of 45,X[38]/47,XXX[2]. When follow-up at age nine months, the neonate was normal in development. FISH analysis on 102 buccal mucosal cells showed 11% (11/102 cells) mosaicism for monosomy X, 12% (12/102 cells) mosaicism for triple X and 77% (79/102 cells) mosaicism for disomy X. Peripheral blood had a karyotype of 45,X[30]/47,XXX[10]. CONCLUSION: 45,X/47,XXX at amniocentesis may detect disomy X cell line by FISH analysis and can be associated with postnatal progressive decrease of the aneuploid cell lines, increase of the disomy X cell line and a favorable outcome.

Mosaic trisomy 16 at amniocentesis in a pregnancy associated with positive non-invasive prenatal testing for trisomy 16, placental trisomy 16, intrauterine growth restriction, intrauterine fetal death, cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes, and prenatal progressive decrease of the aneuploid cell line.

OBJECTIVE: We present mosaic trisomy 16 at amniocentesis in a pregnancy associated with positive non-invasive prenatal testing (NIPT) for trisomy 16, placental trisomy 16, intrauterine growth restriction (IUGR), intrauterine fetal death (IUFD), cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes and uncultured amniocytes, and prenatal progressive decrease of the aneuploid cell line. CASE REPORT: A 26-year-old, primigravid woman underwent amniocentesis at 17 weeks of gestation because of positive NIPT for trisomy 16 at 12 weeks of gestation. Amniocentesis revealed a karyotype of 47,XX,+16 [10]/46,XX[17], and simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed the result of arr (16) × 3 [0.43] consistent with 43% mosaicism for trisomy 16. She was referred for genetic counseling at 19 weeks of gestation, and a fetus with IUGR was noted to have a size equivalent to 16 weeks of gestation. At 23 weeks of gestation, the fetus manifested oligohydramnios, fetal cardiomegaly and severe IUGR (fetal size equivalent to 20 weeks of gestation). Repeat amniocentesis revealed a karyotype of 46,XX (20/20 colonies) in cultured amniocytes and mosaic trisomy 16 by aCGH in uncultured amniocytes. aCGH analysis on uncultured amniocytes revealed the result of arr 16p13.3q24.3 × 2.3, consistent with 30% (log2 ratio = 0.2) mosaicism for trisomy 16. Quantitative fluorescence polymerase chain reaction (QF-PCR) assays on the DNA extracted from parental bloods and uncultured amniocytes excluded uniparental disomy (UPD) 16. The parental karyotypes were normal. IUFD was noted at amniocentesis. The pregnancy was subsequently terminated, and a 288-g female fetus was delivered with no phenotypic abnormalities. The umbilical cord had a karyotype of 46,XX (40/40 cells), and the placenta had a karyotype of 47,XX,+16 (40/40 cells). QF-PCR assays of the placenta confirmed a maternal origin of trisomy 16. CONCLUSION: Mosaic trisomy 16 at amniocentesis can be associated with positive NIPT for trisomy 16, placental trisomy 16, IUGR, IUFD, cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes, and prenatal progressive decrease of the aneuploid cell line.

High-level mosaic trisomy 14 at amniocentesis in a pregnancy associated with congenital heart defects and intrauterine growth restriction on fetal ultrasound.

OBJECTIVE: We present high-level mosaic trisomy 14 at amniocentesis in a pregnancy associated with congenital heart defects (CHD) and intrauterine growth restriction (IUGR). CASE REPORT: A 34-year-old, primigravid woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. This pregnancy was conceived by in vitro fertilization and embryo transfer (IVF-ET). Amniocentesis revealed a karyotype of 47,XX,+14[9]/46,XX[13], consistent with 40.9% (9/22 colonies) mosaicism for trisomy 14. Simultaneous array comparative genomic hybridization (aCGH) on the DNA extracted from uncultured amniocytes revealed 61% mosaicism for trisomy 14. Prenatal ultrasound at 22 weeks of gestation showed a malformed fetus with double outlet of right ventricle (DORV), ventricular septal defect (VSD), pulmonary stenosis and severe IUGR with the growth parameters equivalent to 18 weeks of gestation. The pregnancy was terminated at 23 weeks of gestation, and a 278-g female fetus was delivered with facial dysmorphism of hypertelorism, low-set small ears and wide depressed nasal bridge. Quantitative fluorescent polymerase chain reaction (QF-PCR) analysis on the DNA extracted from parental bloods, cord blood, umbilical cord and placenta confirmed a maternal origin of the extra chromosome 14 and excluded uniparental disomy (UPD) 14. The umbilical cord had a karyotype of 47,XX,+14[7]/ 46,XX[13], and the placenta had a karyotype of 47,XX,+14[4]/46,XX[36]. CONCLUSIONS: High-level mosaic trisomy 14 at amniocentesis can be associated with abnormal ultrasound findings of CHD and IUGR.

Low-level mosaic double trisomy involving trisomy 6 and trisomy 20 (48,XY,+6,+20) at amniocentesis without uniparental disomy (UPD) 6 and UPD 20 in a pregnancy associated with a favorable outcome.

OBJECTIVE: We present low-level mosaic double trisomy involving trisomy 6 and trisomy 20 (48,XY,+6,+20) at amniocentesis without uniparental disomy (UPD) 6 and UPD 20 in a pregnancy associated with a favorable outcome. CASE REPORT: A 38-year-old woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 48,XY,+6,+20[2]/46,XY[15]. Repeat amniocentesis at 20 weeks of gestation revealed a karyotype of 48,XY,+6,+20[6]/46,XY[43], and simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed the result of arr (X,Y) × 1, (1-22) × 2 with no genomic imbalance. At 22 weeks of gestation, the woman underwent cordocentesis which revealed karyotype of 46,XY (60/60 cells). At 26 weeks of gestation, the woman underwent the third amniocentesis which revealed a karyotype of 48,XY,+6,+20[5]/46,XY[30], and simultaneous aCGH analysis on the DNA extracted from uncultured amniocytes revealed the result of arr (1-22) × 2, X × 1, Y × 1 without genomic imbalance. The parental karyotypes and prenatal ultrasound were normal. Polymorphic marker analysis using the DNAs extracted from uncultured amniocytes and parental bloods excluded UPD 6 and UPD 20. Interphase fluorescence in situ hybridization (FISH) analysis on 100 uncultured amniocytes detected double trisomy 6 and trisomy 20 in 10 cells, consistent with 10% (10/100 cells) mosaicism for double trisomy 6 and trisomy 20. The woman was encouraged to continue the pregnancy, and a phenotypically normal 3328-g male baby was delivered at 38 weeks of gestation. The cord blood, umbilical cord and the placenta had a karyotype of 46,XY (40/40 cells). CONCLUSION: Low-level mosaic double trisomy involving trisomy 6 and trisomy 20 at amniocentesis without UPD 6 and UPD 20 can be associated with a favorable fetal outcome.

Mosaic 46,XY,dup(14) (q12q22.3)/46, XY at amniocentesis in a pregnancy associated with a favorable fetal outcome and cytogenetic discrepancy in various tissues.

OBJECTIVE: We present mosaic 46,XY,dup (14) (q12q22.3)/46, XY at amniocentesis in a pregnancy associated with a favorable fetal outcome and cytogenetic discrepancy in various tissues. CASE REPORT: A 41-year-old, primigravid woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. This pregnancy was conceived by in vitro fertilization and embryo transfer. Cytogenetic analysis on cultured amniocytes revealed a karyotype of 46,XY, dup (14) (q12q22.3)[7]/46,XY [13], and simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed arr 14q12q22.3 × 2-3 with 25% mosaicism for partial 14q duplication. She was referred for genetic counseling. Prenatal ultrasound and parental karyotypes were normal. Repeat amniocentesis at 22 weeks of gestation revealed a karyotype of 46,XY,dup (14) (q12q22.3)[6]/46,XY [14], and in uncultured amniocytes, quantitative fluorescence polymerase chain reaction (QF-PCR) analysis excluded uniparental disomy (UPD) 14, aCGH revealed arr 14q12q22.3 × 2.3 with 30% mosaicism for dup (14) (q12q22.3), and interphase fluorescence in situ hybridization (FISH) showed 19.4% (24/124 cells) mosaicism for partial 14q duplication. She was encouraged to continue the pregnancy, and a 2450-g phenotypically normal male baby was delivered at 40 weeks of gestation. The karyotypes of cord blood, umbilical cord and placenta were 46,XY,dup (14) (q12q22.3)[14]/46,XY [26], 46,XY,dup (14) (q12q22.3)[7]/46,XY [33] and 46,XY,dup (14) (q12q22.3)[3]/46,XY [37], respectively. When follow-up at age four months, the neonate was phenotypically normal. The karyotype of peripheral blood was 46,XY,dup (14) (q12q22.3)[27]/46,XY [13], and interphase FISH analysis on 105 buccal mucosal cells detected partial 14q duplication signals in 5 cells (4.8% mosaicism). When follow-up at age nine months, the neonate was phenotypically normal. The karyotype of peripheral blood was 46,XY,dup (14) (q12q22.3)[25]/46,XY [15]. CONCLUSION: Mosaic dup (14) (q12q22.3) with a normal cell line at amniocentesis may be a benign condition, and can be associated with a favorable fetal outcome and cytogenetic discrepancy in various tissues.

Mosaic 45,X/46, XX at amniocentesis with high-level mosaicism for 45,X in a pregnancy with a favorable fetal outcome and postnatal decrease of the 45,X cell line.

OBJECTIVE: We present mosaic 45,X/46, XX at amniocentesis with high-level mosaicism for 45,X in a pregnancy with a favorable fetal outcome and postnatal decrease of the 45,X cell line. CASE REPORT: A 20-year-old, primigravid woman underwent amniocentesis at 17 weeks of gestation because of the non-invasive prenatal testing (NIPT) result of -4.82 Z score in sex chromosome at 12 weeks of gestation suggestive of Turner syndrome in the fetus. Amniocentesis revealed a karyotype of 45,X [18]/46,XX [15], and simultaneous multiplex ligation-dependent probe amplification (MLPA) on the DNA extracted from uncultured amniocytes showed mosaic Turner syndrome. Prenatal ultrasound and parental karyotypes were normal. She was referred for genetic counseling at 24 weeks of gestation, and continuing pregnancy was encouraged. At 39 weeks of gestation, a 2550-g phenotypically normal female baby was delivered. The karyotypes of cord blood, umbilical cord and placenta were 45,X [24]/46,XX [16], 45,X [23]/46,XX [17] and 45,X [28]/46,X,del(X) (q23)[12], respectively. When follow-up at age two months, the neonate was phenotypically normal in development. The peripheral blood had a karyotypes of 45,X [16]/46,XX [24]. Interphase fluorescence in situ hybridization (FISH) analysis on 103 buccal mucosal cells showed normal disomy X signals in all cells. CONCLUSION: High-level mosaicism for 45,X in 45,X/46, XX at amniocentesis can be associated with a favorable fetal outcome, cytogenetic discrepancy in various tissues, and postnatal decrease of the 45,X cell line.

Molecular cytogenetic characterization of de novo concomitant distal 8p deletion of 8p23.3p23.1 and Xp and Xq deletion of Xp22.13q28 due to an unbalanced X;8 translocation detected by amniocentesis.

OBJECTIVE: We present molecular cytogenetic characterization of de novo concomitant distal 8p deletion of 8p23.3p23.1 and Xp and Xq deletion of Xp22.13q28 due to an unbalanced X;8 translocation detected by amniocentesis. CASE REPORT: A 33-year-old primigravid woman underwent amniocentesis at 18 weeks of gestation because of a Down syndrome risk of 1/52 at the first-trimester maternal serum screening calculated from 0.29 multiples of the median (MoM) of pregnancy associated plasma protein-A (PAPP-A), 1.14 MoM of free ß-hCG and 0.46 MoM of placental growth factor (PlGF). Amniocentesis revealed a karyotype of 45,X,add(8)(p23.1). The parental karyotypes were normal. Array comparative genomic hybridization (aCGH) analysis on the DNA extracted from cultured amniocytes revealed a 137-Mb deletion of Xp22.13q28 and a 10.53-Mb deletion of 8p23.3p23.1. The karyotype thus was 45,X,der(8)t(X;8)(p22.13;p23.1). Prenatal ultrasound revealed pericardial effusion and skin edema. The pregnancy was subsequently terminated, and a 568-g malformed fetus was delivered with hypertelorism and low-set ears. The cord blood had a karyotype of 45,X,der(8)t(X;8)(p22.13;p23.1). aCGH analysis of the cord blood revealed the result of arr [GRCH37 (hg19)] 8p23.3p23.1 (191,530-10,724,642) × 1.0, arr Xp22.13q28 (18,194,098-155,232,907) × 1.0. CONCLUSION: aCGH analysis is useful elucidating the genetic nature of an aberrant chromosome with an additional maternal of unknown origin attached to a chromosome terminal region.

Cytogenetic discrepancy between uncultured amniocytes and cultured amniocytes in mosaic trisomy 18 at amniocentesis in a pregnancy with a favorable fetal outcome and maternal uniparental disomy 18.

OBJECTIVE: We present prenatal diagnosis of mosaic trisomy 18 in a pregnancy with a favorable fetal outcome and maternal uniparental disomy 18. CASE REPORT: A 38-year-old, primigravid woman underwent the first amniocentesis at 16 weeks of gestation because advanced maternal age. Amniocentesis revealed a karyotype of 46,XX [22/22] in cultured amniocytes, and 36% mosaicism for trisomy 18 and a maternally inherited Xp22.31 microdeletion by array comparative genomic hybridization (aCGH) in uncultured amniocytes. The second amniocentesis at 18 weeks of gestation revealed 47,XX,+18 [14]/46,XX [36] in cultured amniocytes and 36% mosaicism for trisomy 18 by multiplex ligation-dependent probe amplification (MLPA) P095 in cultured amniocytes. Prenatal ultrasound was normal. The parents were phenotypically normal. The third amniocentesis at 23 weeks of gestation revealed 47,XX,+18 [3]/46,XX [17] in cultured amniocytes, and in uncultured amniocytes, aCGH revealed 45%-50% mosaicism for trisomy 18, interphase fluorescence in situ hybridization (FISH) revealed 36% (36/100 cells) mosaicism for trisomy 18, and quantitative fluorescent polymerase chain reaction (QF-PCR) showed mosaic maternal uniparental heterodisomy for chromosome 18 and mosaic trisomy 18 of maternal origin. The fourth amniocentesis at 32 weeks of gestation revealed a karyotype of 46,XX [20/20] in cultured amniocytes, and in uncultured amniocytes, aCGH revealed 50%-60% mosaicism for trisomy 18, FISH revealed 21.8% (22/101 cells) mosaicism for trisomy 18, and non-invasive prenatal testing (NIPT) showed chromosome 18 gene dosage increase in the maternal blood. At 34 weeks of gestation, a 1480-g phenotypically normal baby was delivered. The cord blood had 47,XX,+18 [10]/46,XX [30]. The umbilical cord had 47,XX,+18 [4]/46,XX [36]. The placenta had 47,XX,+18 [40/40], and QF-PCR analysis confirmed trisomy 18 of maternal origin. When follow-up at age four months, the neonate was phenotypically normal, FISH analysis on buccal mucosal cells revealed 2% (2/100 cells) mosaicism for trisomy 18, and the peripheral blood had 47,XX,+18 [18]/46,XX [22]. When follow-up at age eight months, the neonate had normal development, the peripheral blood had 47,XX,+18 [15]/46,XX [25], and the buccal mucosal cells showed maternal uniparental heterodisomy for chromosome 18. CONCLUSION: Cytogenetic discrepancy may occur between uncultured and cultured amniocytes in mosaic trisomy 18 at amniocentesis. Cultured amniocytes may present progressive decrease in the levels of mosaicism for trisomy 18 as the fetus grows. Mosaic trisomy 18 at amniocentesis can be associated with a favorable outcome.

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

OBJECTIVE: We present prenatal diagnosis and molecular cytogenetic characterization of a familial small supernumerary marker chromosome (sSMC) derived from the acrocentric chromosome 14/22. CASE REPORT: A 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). CONCLUSION: FISH 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.

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.

OBJECTIVE: We 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 REPORT: A 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. CONCLUSION: Cytogenetic 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.

Molecular cytogenetic characterization of a de novo small supernumerary marker chromosome derived from chromosome 15 in a pregnancy with incidental detection of a maternal Robertsonian translocation of 45,XX,der(13;14) (q10;q10).

OBJECTIVE: We present molecular cytogenetic characterization of a small supernumerary marker chromosome (sSMC) derived from chromosome 15 in a pregnancy with incidental detection of a maternal Robertsonian translocation of 45,XX,der(13; 14) (q10; q10). CASE REPORT: A 37-year-old, primigravid woman underwent amniocentesis at 16 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 47,XY,+mar. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes showed the result of no genomic imbalance or arr (1-22) × 2, (X,Y) × 1. Cytogenetic analysis of the parents showed a karyotype of 45,XX,der(13; 14) (q10; q10) in the mother and a karyotype of 46,XY in the father. Prenatal ultrasound was unremarkable. At 38 weeks of gestation, a 2790-g phenotypically normal male baby was delivered. The cord blood had a karyotype of 47,XY,+mar. Metaphase fluorescence in situ hybridization (FISH) analysis showed the result of +mar.ish dic(15) (D15Z1++, SNRPN-, PML-) (18/20). The extra chromosome was derived from chromosome 15. CONCLUSION: Metaphase FISH analysis is useful for the identification of the origin of an sSMC in the presence of no genomic imbalance at aCGH analysis. Prenatal diagnosis of a de novo sSMC may be associated with a Robertsonian translocation in the parents, and parental cytogenetic analysis is necessary under such a circumstance.

Prenatal diagnosis of maternal uniparental disomy 21 in association with low-level mosaic trisomy 21 at amniocentesis in a pregnancy associated with intrauterine growth restriction and a favorable outcome.

OBJECTIVE: We present prenatal diagnosis of maternal uniparental disomy (UPD) 21 in association with low-level mosaic trisomy 21 at amniocentesis in a pregnancy associated with intrauterine growth restriction (IUGR) and a favorable outcome. CASE REPORT: A 42-year-old, gravida 2, para 0, woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis initially revealed a karyotype of 46,XX in 20/20 colonies of cultured amniocytes. Simultaneous array comparative genomic hybridization (aCGH) analysis on uncultured amniocytes revealed a result of arr [GRCh37] (21) × 3 [0.16], (X) × 2, compatible with mosaic trisomy 21. After extensive investigation, the final result of conventional cytogenetic analysis of cultured amniocytes was 47,XX,+21[1]/46,XX[40]. The parental karyotypes were normal. Repeat amniocentesis was performed at 21 weeks of gestation. The cultured amniocytes had a karyotype of 47,XX,+21[3]/46,XX[27] and the uncultured amniocytes had a mosaic trisomy 21 level of 8.8% (10/114 cells) by interphase fluorescence in situ hybridization (FISH), a mosaic trisomy 21 level of 10% (log2 ratio = 0.08) by aCGH, and maternal UPD 21 by polymorphic DNA marker analysis. Prenatal ultrasound revealed IUGR. At 38 weeks of gestation, a phenotypically normal 2695-g baby was delivered. The cord blood and umbilical cord had the karyotype of 46,XX and maternal UPD 21. The placenta had a karyotype of 47,XX,+21[8]/46,XX[32] and a maternal origin of trisomy 21. Postnatal FISH analysis on 101 buccal mucosal cells showed 6.9% (7/101 cells) mosaicism compared with 2% (2/100 cells) in the normal control. The baby was doing well at age four months. CONCLUSION: Pregnancy with low-level mosaic trisomy 21 and maternal UPD 21 at amniocentesis can be associated with IUGR and a favorable outcome. Fetuses with maternal UPD 21 can be associated with mosaic trisomy 21 at amniocentesis.

Prenatal diagnosis of mosaic trisomy 16 by amniocentesis in a pregnancy associated with abnormal first-trimester screening result (low PAPP-A and low PlGF), intrauterine growth restriction and a favorable outcome.

OBJECTIVE: We present prenatal diagnosis of mosaic trisomy 16 by amniocentesis in a pregnancy associated with an abnormal first-trimester screening result, intrauterine growth restriction (IUGR) and a favorable outcome. CASE REPORT: A 27-year-old woman underwent amniocentesis at 18 weeks of gestation because of an abnormal first-trimester screening result with maternal serum free ß-hCG of 1.474 multiples of the median (MoM), pregnancy associated plasma protein-A (PAPP-A) of 0.122 MoM and placental growth factor (PlGF) of 0.101 MoM, and a Down syndrome risk of 1/45. Amniocentesis revealed a karyotype of 47,XY,+16 [9]/46,XY [16] and an abnormal array comparative genomic hybridization (aCGH) result of arr (16) × 3 [0.54] compatible with 54% mosaicism for trisomy 16 in uncultured amniocytes. At 24 weeks of gestation, repeat amniocentesis revealed a karyotype of 47,XY,+16 [4]/46,XY [16] and an aCGH result of arr 16p13.3q24.3 (96,766-90,567,357) × 2.25 with a log2 ratio = 0.2 compatible with 20-30% mosaicism for trisomy 16 in uncultured amniocytes. Quantitative fluorescent polymerase chain reaction (QF-PCR) excluded uniparental disomy (UPD) 16. Interphase fluorescence in situ hybridization (FISH) analysis on uncultured amniocytes revealed 19.4% (12/62 cells) mosaic trisomy 16. Prenatal ultrasound revealed IUGR. At 36 weeks of gestation, a phenotypically normal baby was delivered with a body weight of 1900 g. The cord blood had a karyotype of 46,XY. QF-PCR analysis confirmed biparentally inherited disomy 16 in the cord blood and maternal-origin of trisomy 16 in the placenta. When follow-up at age two months, FISH analysis on 101 buccal mucosal cells and 32 urinary cells revealed no signal of trisomy 16. CONCLUSION: Mosaic trisomy 16 at amniocentesis can be associated with IUGR and an abnormal first-trimester screening result with low PAPP-A and low PlGF. Mosaic trisomy 16 without UPD 16 at amniocentesis can have a favorable outcome, and the abnormal triosmy 16 cell line may disappear after birth.

Prenatal diagnosis of recurrent mosaic ring chromosome 13 of maternal origin.

OBJECTIVE: We present prenatal diagnosis of recurrent mosaic ring chromosome 13 [r(13)] of maternal origin. CASE REPORT: A 27-year-old woman underwent amniocentesis at 17 weeks of gestation because of a past history of fetal abnormality caused by mosaic r(13) in the previous fetus associated with fetal intrauterine growth restriction (IUGR), a karyotype of 46,XY,r(13)[23]/45,XY,-13[10]/46,XY,idic r(13)[2] and a maternal origin of abnormal r(13). The parental karyotypes were normal. During this pregnancy, amniocentesis revealed a karyotype of 46,XX,r(13)[12]/45,XX,-13[8] and a 22.80-Mb deletion of chromosome 13q31.3-q34. The pregnancy was subsequently terminated, and a malformed fetus was delivered with craniofacial dysmorphism. Repeat amniocentesis revealed a karyotype of 46,XX,r(13)(p11.1q31)[18]/45,XX,-13[12]. The placenta had a karyotype of 46,XX,r(13)(p11.1q31)[27]/45,XY,-13[13]. Polymorphic DNA marker analysis using the DNA derived from the parental bloods and umbilical cord confirmed a maternal origin of the abnormal r(13). CONCLUSION: Prenatal diagnosis of mosaic r(13) in consecutive pregnancies should raise a suspicion of parental gonadal mosaicism, and polymorphic DNA marker analysis is useful for determination of the parental origin of recurrent aneuploidy under such a circumstance.

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.

OBJECTIVE: We 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 REPORT: A 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. CONCLUSION: In 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 of mosaicism for double aneuploidy of 47,XXY and trisomy 7 (48,XXY,+7) at amniocentesis in a pregnancy with a favorable outcome.

OBJECTIVE: We present prenatal diagnosis of mosaicism for double aneuploidy of 47, XXY and trisomy 7 (48,XXY,+7) at amniocentesis in a pregnancy with a favorable outcome. CASE REPORT: A 33-year-old woman underwent amniocentesis at 17 weeks of gestation because of an increased risk for Down syndrome in maternal serum screening. Amniocentesis revealed a karyotype of 48,XXY,+7[8]/46,XY[16]. Simultaneous array comparative genomic hybridization (aCGH) analysis on uncultured amniocytes revealed the result of arr [GRCh37] (7) × 3 [0.54], (X) × 2 [0.52], (Y) × 1, compatible with trisomy 7 mosaicism and Klinefelter syndrome mosaicism. The parental karyotypes and prenatal ultrasound findings were normal. Repeat amniocentesis performed at 23 weeks of gestation revealed a karyotype of 48,XXY,+7[13]/46,XY[7]. Simultaneous molecular cytogenetic analyses on uncultured amniocytes revealed 30% mosaicism for 48,XXY,+7 by aCGH and 37% (37/100 cells) mosaicism for trisomy 7 and disomy X by interphase fluorescence in situ hybridization (FISH) analysis. Polymorphic DNA marker analysis excluded uniparental disomy (UPD) 7 and indicated a maternal origin of the chromosome aberration. The pregnancy was continued to 39 weeks of gestation, and a 3070-g healthy male baby was delivered. The cord blood had a karyotype of 46,XY, the umbilical cord had a karyotype of 48,XXY,+7[3]/46,XY[37], and the placenta had a karyotype of 48,XXY,+7. At age one month, the neonate was phenotypically normal, and interphase FISH analysis revealed 4.8% (5/105 cells) mosaicism on buccal mucosal cells and 8.9% (8/90 cells) mosaicism on urinary cells for trisomy 7 and disomy X, compared with 2% in normal control. Interphase FISH analysis on buccal mucosal cells at age two months revealed normal findings in 100/100 cells. CONCLUSION: Mosaic 48,XXY,+7 at amniocentesis without UPD 7 can be associated with a favorable fetal outcome. Cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes may occur in mosaic 48,XXY,+7 at amniocentesis.