Prenatal Diagnosis and Molecular Cytogenetic Characterization of a Small Supernumerary Marker Chromosome Derived from Chromosome 18 and Associated With a Reciprocal Translocation Involving Chromosomes 17 And 18

SummaryObjectivePrenatal diagnosis of small supernumerary marker chromosomes (sSMC) gives rise to difficulties in genetic counseling, and requires molecular cytogenetic technologies such as spectral karyotyping, fluorescence in situ hybridization, multicolor-fluorescence in situ hybridization, or array-comparative genomic hybridization to identify the nature of the aberrant chromosome. We report such a case associated with a reciprocal translocation.Materials, Methods and ResultsA 36-year-old woman, gravida 7, para 1, abortus 5, was referred for amniocentesis at 18 weeks of gestation because of advanced maternal age. Amniocentesis revealed a reciprocal translocation between chromosomes 17q and 18q and an sSMC. The karyotype was 47,XY,t(17;18)(q11.1;q11.2), +mar. Chromosome preparations from blood lymphocytes revealed that she had the same reciprocal translocation and sSMC. Spectral karyotyping showed that the sSMC was derived from the centromeric region of chromosome 18, and there was a reciprocal translocation between chromosomes 17 and 18. The derivative chromosome 17 had positive 17p terminal (17pTEL) and chromosome 17 centromeric (cep17) signals but did not have a positive chromosome 18 centromeric signal (cep18). The derivative chromosome 18 had positive 18p terminal (18pTEL), chromosome 18 centromeric (cep18) and cep17 signals. The sSMC had only a positive cep18 signal. These findings suggested that a breakpoint occurred at 17q11.1 and another at 18q11.2 during translocation, and the sSMC originated from chromosome 18. The karyotype of the fetus was thus 47,XY,t(17;18)(q11.1;q11.2), +mar.ish der(17)t(17;18)(q11.1;q11.2)(17pTEL+,D17Z1+),der(18)t(17;18)(q11.1;q11.2)(18pTEL+,D18Z1+,D17Z1+), + der(18)(D18Z1+). Oligonucleotide-based array comparative genomic hybridization demonstrated no gain or loss of the gene dosage on chromosomes 17 and 18.ConclusionOur case adds to the reported cases of sSMCs derived from the centromeric region of chromosome 18 without phenotypic consequences

Digynic triploidy in a fetus presenting with semilobar holoprosencephaly

Objective: We present digynic triploidy in a fetus with semilobar holoprosencephaly (HPE). Case report: A 32-year-old, gravid 1, para 0, woman underwent prenatal ultrasound examination at 12 weeks of gestation, and the ultrasound showed relative macrocephaly, a small non-cystic placenta, and a fetus with absent nasal bone and semilobar HPE. The pregnancy was terminated subsequently, and a 50-g fetus was delivered with a relatively enlarged head and premaxillary agenesis. The placenta was small and non-cystic. Postnatal cytogenetic analysis of the umbilical cord revealed a karyotype of 69, XXX. Postnatal DNA marker analysis using quantitative fluorescent polymerase chain reaction assays and the polymorphic short tandem repeat markers for chromosome 18 and 20 on the placental tissues showed a diallelic pattern with a dosage of 1:2 (paternal allele to maternal allele ratio), indicating a maternal origin of the triploidy. Conclusion: Fetuses with digynic triploidy may present relative macrocephaly, semilobar HPE and a small placenta on prenatal ultrasound. Keywords: Semilobar holoprosencephaly, Digynic triploid

Chromosomal deletions detected at amniocentesis

[[abstract]]OBJECTIVE: The aim of this study is to present the incidence, prenatal and postnatal findings, and modes of ascertainment in chromosomal deletions detected at amniocentesis. MATERIALS AND METHODS: We reviewed all the cases with chromosomal deletions, which were detected by amniocentesis in Mackay Memorial Hospital, Taipei, Taiwan, between January 1987 and December 2012. Data on the locations and types of deletion, reasons for performing amniocentesis, maternal age, gestational age at amniocentesis, fetal karyotypes, inheritance of deletions, and relative prenatal findings were collected. RESULTS: Amniocentesis was performed in 33,305 cases within this period of time. Among these, 31 cases of chromosomal deletions were considered for the study. The mean gestational age at amniocentesis was 21.0 weeks (range from 15 weeks to 32 weeks) and the mean maternal age at amniocentesis was 32.1 years (range from 26 years to 37 years). Nineteen cases (61.3%) manifested fetal structural abnormalities on ultrasound, nine (29.0%) presented no ultrasound abnormalities, and three had an unknown status. The main modes of ascertainment included abnormal ultrasound findings in 10 cases (32.2%), advanced maternal age in 11 cases (35.5%), abnormal maternal serum screening results in six cases (19.6%), and other reasons in four cases (13.0%). Of the 27 cases with known inheritance, the deletion was inherited in two (6.6%) and de novo in 25 (92.6%). Males accounted for 11 (35.5%) and females for 20 (64.5%) cases. Chromosomal deletions are more often to occur in chromosomal 5(4 cases, 12.9%), chromosomal 18 (4 cases, 12.9%), chromosomal 4 (3 cases, 9.7%), chromosomal 7 (3 cases, 9.7%), chromosomal 10 (3 cases, 9.7%), chromosomal 11 (3 cases, 9.7%), and chromosomal 1 (2 cases, 6.5%). There were four cases of chromosomal mosaicism: two involved chromosome 5, one involved chromosome 10, and one involved chromosome 18. Twenty-three cases (74.2%) had terminal deletions and the other eight cases (26.7%) had interstitial-type deletions. CONCLUSION: In summary, we have presented the results of prenatal diagnosis for chromosomal deletions using amniocentesis. Chromosomal deletions are more likely to occur in females and more often in chromosomal 5p and 18q. Prenatal diagnosis at amniocentesis is frequently associated with advanced maternal age, abnormal ultrasound findings, and abnormal maternal serum screening. The frequency of ascertainment in chromosome deletion seems to be directly correlated with advanced maternal age and abnormal ultrasound findings. In cases with terminal deletions, prenatal ultrasound plays a more important role for prenatal diagnosis. Copyright © 2014. Published by Elsevier B.V

Unbalanced and Balanced Heterologous Acrocentric Rearrangements Involving Chromosome 21 at Amniocentesis

SummaryObjectiveTo present unbalanced and balanced heterologous acrocentric rearrangements involving chromosome 21 at amniocentesis.Materials and MethodsBetween January 1987 and September 2009, 31,194 amniocenteses were performed at Mackay Memorial Hospital, Taipei, Taiwan. Two cases with an unbalanced heterologous acrocentric rearrangements involving chromosome 21 from two families and seven cases with balanced heterologous acrocentric rearrangements involving chromosome 21 from five families were diagnosed and investigated.ResultsWe detected rob(14q21q),+21 (one case), rob(13q21q),+21 (one case), rob(14q21q) (four cases), rob(13q21q) (one case) and rob(15q21q) (two cases). Of the nine cases that underwent parental cytogenetic investigation, one was de novo and eight were inherited (five maternal and three paternal). The six families with an inherited acrocentric rearrangement included rob(14q21q) (three families), rob(13q21q) (two families) and rob(15q21q) (one family). Of these six families, three had a known parental carrier status before the first amniocentesis, while the other three were aware of their parental carrier status only after prenatal diagnosis of a fetus with a heterologous acrocentric rearrangement. The seven fetuses with a balanced heterologous acrocentric rearrangement were inherited from two paternal carriers of rob(14q21q), one maternal carrier of rob(14q21q), one maternal carrier of rob(13q21q), and one maternal carrier of rob(15q21q). No uniparental disomy 14 was detected in any of the three cases with rob(14q21q) tested for uniparental disomy.ConclusionConcerning heterologous acrocentric rearrangements involving chromosome 21, the frequency of unbalanced rearrangements was 0.0064% and that of balanced rearrangements was 0.0224% at amniocentesis. In this study, rob(14q21q) was the most common, and rob(13q21q) and rob(15q21q) were the second most common rearrangements. Of the six families with an inherited heterologous acrocentric rearrangement involving chromosome 21, 50% (3/6) were aware of their parental carrier status only after prenatal diagnosis of a fetus with a translocation by amniocentesis

Higher male prevalence of chromosomal mosaicism detected by amniocentesis

Objective: To present the calculated frequencies, male to female sex-ratio, and modes of ascertainments in different levels of chromosomal mosaicism (CM) detected at amniocentesis. Materials and methods: This's a 10-years retrospective study between January 2008 and December 2017 and there were 13,752 cases of amniocentesis performed in MacKay Memorial Hospital, Taipei, Taiwan. Eight hundred and thirty four cases of CM were collected in this study. We reviewed their types of chromosomal abnormalities of mosaicism, the modes of ascertainment (including: advanced maternal age, abnormal ultrasound findings, abnormal maternal serum screening result, and other reasons), maternal age, gestational age at amniocentesis, fetal gender, and perinatal findings. After amniocentesis, in situ culture was performed and the results of karyotype with CM were divided in to three levels. Results: In our sample of 13,752 amniocentesis, 834 cases with all levels of CM were collected in this study. Of them, there were 562 cases (4.09%) with level I mosaicism, 207 cases (1.51%) of level II mosaicism, and 65 cases (0.47%) of level III mosaicism (Table 1). In the group of advanced of maternal age (AMA), their calculated frequencies, 4.18% in level I, 1.46% in level II and 0.41% in level III, were very similar to those in total cases (p value = 0.206) without statistical significance. In the group of abnormal ultrasound findings, the calculated frequency was much higher in level III (0.87%), however, there was no statistical significance because of the small numbers of level III. In our cases of amniocentesis, the case numbers of male case (50.20%) is very similar to female (49.80%), and the male to female ratio was 1.01. But, we found more cases of male with CM (444 cases) than female (390 cases). The sex-ratio in different levels’ calculated frequencies of CM showed similar in level I, and male prevalence was found in level II and III with statistical significance (p value = 0.022). The male prevalence also revealed in both numerical and structural abnormalities in level II and level III, but no difference in the cases of level I. Conclusion: In conclusion, our observation showed a novel finding of higher male prevalence of CM in level II and III, and both in numerical and structural abnormalities. It's consistent with the theory of better survival in male embryo after partial self-correction of initial chromosomal aberrations, male-specific selection against chromosomal abnormalities

Prenatal diagnosis of a familial 15q11.2 (BP1-BP2) microdeletion encompassing TUBGCP5, CYFIP1, NIPA2 and NIPA1 in a fetus with ventriculomegaly, microcephaly and intrauterine growth restriction on prenatal ultrasound

Objective: We present prenatal diagnosis of a 15q11.2 (BP1-BP2) microdeletion encompassing TUBGCP5, CYFIP1, NIPA2 and NIPA1 in a fetus with ventriculomegaly, microcephaly and intrauterine growth restriction (IUGR) on prenatal ultrasound. Case report: A 30-year-old, gravida 3, para 2, woman was referred to the hospital for amniocentesis because of fetal ventriculomegaly on prenatal ultrasound. Her husband was 31 years old. The couple had two healthy daughters, and there was no family history of mental disorders and congenital malformations. Amniocentesis revealed a karyotype of 46,XX. Array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed a 451.89-kb 15q11.2 microdeletion or arr 15q11.2 (22,765,628–23,217,514) × 1.0 [GRCh37 (hg19)] encompassing TUBGCP5, CYFIP1, NIPA2 and NIPA1. The parental karyotypes were normal. aCGH analysis on the DNAs extracted from parental bloods revealed a 402-kb 15q11.2 microdeletion or arr 15q11.2 (22,815,577-23,217,514) × 1.0 (hg19) encompassing TUBGCP5, CYFIP1, NIPA2 and NIPA1 in the phenotypically normal father. The mother did not have any genomic imbalance. Level II ultrasound at 21 weeks of gestation revealed microcephaly and IUGR. The parents elected to terminate the pregnancy at 22 weeks of gestation, and a female fetus was delivered with a body weight of 448 g (10th centile) and a body length of 26 cm (3rd–10th centile) but no gross abnormalities. Conclusion: Fetuses with a 15q11.2 (BP1-BP2) microdeletion may present ventriculomegaly, microcephaly and IUGR on prenatal ultrasound, and aCGH is helpful for prenatal diagnosis under such a circumstance. Keywords: 15q11.2 (BP1-BP2) deletion, Microcephaly, Prenatal diagnosis, Ventriculomegal