Direct preparations from chorionic villi–relationship between villous morphology and mitotic index

It has been postulated that chorionic villi with abundant sprouts have a higher mitotic index and are therefore preferable for obtaining direct chromosome preparations from chorionic villus samples. This theory was tested by correlating villous morphology with mitotic index. Surprisingly, no statistically significant relationship was found. Choice of culture medium, however, was found to be important, with serum-free RPMI yielding a higher mitotic index than 40 per cent FCS in MEM. We conclude that villous morphology, as assessed in this study, is not a major factor in determining the success of direct chromosome preparations.     

Prenatal diagnosis of a double bisatellited marker with an unusual copy number ratio

Prenatal diagnosis, by amniocentesis, revealed mosaicism with respect to a bisatellited, apparently dicentric, DA/DAPI positive, de novo marker. The following cell lines were observed in decreasing order of frequency: 46,XX > 48.XX, + mar, + mar » 47,XX, + mar. The pregnancy was terminated and post-mortem examination revealed an apparently normal fetus. Cytogenetic studies of fetal and placental tissues revealed approximately the same level of mosaicism together with the unusual copy number ratio seen in the amniotic fluid cultures. Non-disjunction at the first post-zygotic mitotic division giving rise to a mosaic: 46,XX/ 48,XX, + mar, + mar followed by subsequent mitotic instability of the marker could account for the unusual copy number ratio.     

Maternal urinary β-core fragment of hCG/creatinine ratios and fetal chromosomal abnormalities in the second trimester of pregnancy

Our aim was to evaluate the potential value of the ratio of the maternal urinary beta-core fragment of human chorionic gonadotropin (βC-hCG) to creatinine (Cr) in discriminating between normal pregnancies and pregnancies associated with fetal chromosomal abnormalities. We hypothesized that pregnancies with fetal chromosomal abnormalities had abnormal quantities of βC-hCG in the urine. The aims of the present study were to investigate retrospectively whether maternal urinary ratios of βC-hCG/Cr are abnormal in women carrying fetuses with chromosome aberrations and to determine normative median values and a reference range for βC-hCG/Cr between 14 and 19 weeks' gestation. Maternal urinary βC-hCG and Cr concentrations were measured in 150 healthy women from 14 to 19 weeks and compared with ten cases of fetal chromosomal abnormalities matched for gestational age. The preliminary cut-off points corresponded to 0·29 multiple of the normal median (MOM) and 2·83 MOM, which were equivalent to the tenth and 90th centiles of the normal range. Of ten cases of fetal chromosomal abnormalities, one out of one (100 per cent) case with trisomy 18 and three of four (75 per cent) cases of variant 9 chromosome had low βC-hCG/Cr (≤0·29 MOM). One of five (20 per cent) cases with Down syndrome had elevated βC-hCG/Cr (≤2·83 MOM). Urinary βC-hCG/Cr ratios obtained in the second trimester may be useful for improved detection efficiency of Down syndrome, trisomy 18, and inversion of chromosome 9. Second-trimester maternal urinary βC-hCG/Cr should be investigated further as a potential marker for fetal chromosome anomalies.     

Prenatal diagnosis of familial ring 21 chromosome

Ring chromosome 21 is a rare chromosome anomaly often associated with mental retardation and dysmorphic features. Less commonly, the ring chromosome can be familial and associated with a normal phenotype. Phenotypically normal female carriers, however, are at increased risk of having children with Down syndrome, mosaic monosomy 21, and variable duplication or deletion of chromosome 21. Because of the relative mitotic and meiotic instability of ring chromosomes, abnormal cytogenetic findings encountered during prenatal diagnosis may not reflect the true genetic status of the fetus. This is a report of a phenotypically normal female carrier of a familial ring 21 chromosome. Prenatal diagnosis on her twin pregnancy revealed a mosaic 46,XX,r(21)(p13;q22) (77 per cent)/45,XX, – 21 in one fetus and a normal male karyotype in the second. The pregnancy was carried to term. Both infants are completely normal, with a non-mosaic ring 21 karyotype from the lymphocytes of one twin. The diagnostic uncertainty and problematic genetic counselling related to fetal cytogenetic abnormalities are the subjects of this report.     

Pregnancy outcome following prenatal diagnosis of an isodicentric X chromosome: first case report

An isodicentric X chromosome, idic (X)(q27) was found in a female fetus during cytogenetic studies performed on amniotic cells due to advanced maternal age. No mosaicism was observed. Although segmental inversion duplications have been described for several other chromosomes, isodicentric chromosomes are reported only for gonosomes. Genetic counselling was based on ultrasound findings, cytogenetic replication studies and published cases of X chromosomes duplications ascertained pre- and postnatally. The pregnancy resulted in the birth of a healthy female infant. Copyright © 2002 John Wiley & Sons, Ltd.