Exclusion of chromosomal mosaicism in prenatal diagnosis

Summary For use in prenatal diagnosis, tables were prepared giving the number of metaphases or clones, respectively, which must be analysed in order to detect fetal mosaicism of a given degree (=percentage of the aberrant cell population) or higher with at least 95% or 99% probability. Different tables are provided for the two techniques of chromosomal preparation: the colony method and the flask method.     

Chromosomal mosaicism detected by karyotyping and chromosomal microarray analysis in prenatal diagnosis

To investigate the incidence and clinical significance of chromosomal mosaicism (CM) in prenatal diagnosis by G-banding karyotyping and chromosomal microarray analysis (CMA). This is a single-centre retrospective study of invasive prenatal diagnosis for CM. From 5758 karyotyping results and 6066 CMA results, 104 foetal cases with CM were selected and analysed further. In total, 50% (52/104) of foetal cases with CM were affected by ultrasound-detectable phenotypes. Regardless of whether they were singleton or twin pregnancies, isolated structural defects in one system (51.35%, 19/37 in singletons; 86.67%, 13/15 in twins) and a single soft marker (18.92%, 7/37 in singletons; 13.33%, 2/15 in twins) were the most common ultrasound anomalies. Mosaic autosomal trisomy (19.23%, 20/104) was the most frequent type, and its rate was higher in phenotypic foetuses (28.85%, 15/52) than in non-phenotypic foetuses (9.62%, 5/52). There was no difference in mosaic fractions between phenotypic and non-phenotypic foetuses based on specimen sources or overall classification. Discordant mosaic results were observed in 16 cases (15.38%, 16/104) from different specimens or different testing methods. Genetic counselling and clinical management regarding CM in prenatal diagnosis remain challenging due to the variable phenotypes and unclear significance. Greater caution should be used in prenatal counselling, and more comprehensive assays involving serial ultrasound examinations, different specimens or testing methods verifications and follow-up should be applied.     

A phenotypically normal liveborn male after prenatal diagnosis of trisomy 20 mosaicism

We report on a case of prenatally diagnosed true trisomy 20 mosaicism in amniocytes. Cytogenetic analysis was performed postnatally on lymphocytes and extra-embryonic tissues. For analysing uroepithelial cells we established a new cell nuclei preparation protocol for FISH (Fluorescence In Situ Hybridization). Trisomy 20 cells could not be confirmed after birth. The origin or trisomy 20 cells in amniotic fluid remains unclear. The phenotypically normal male baby is developing normal.     

Rare case of XX/XY mosaicism and trisomy 13 in early prenatal diagnosis

Coexistence of XX/XY sex mosaicism and autosomal trisomy in prenatal diagnosis is particularly rare. Herein, we report the first, to our knowledge, case of a fetus with cyclopia, ambiguous genitalia and a 47,XX,+13,inv9[47]/47,XY,+13[13] karyotype detected at 13 weeks of gestation after chorionic villus sampling. Molecular analysis after prenatal diagnosis suggests that this is a case of sex mosaicism coexisting with trisomy 13, rather than chimera.     

Pyruvate carboxylase activity in chorionic villi: possibility of application to prenatal diagnosis

Pyruvate carboxylase (PC) activity was assayed in 27 chorionic villi samples (CVS) obtained at 9-12 weeks of gestation. The kinetic properties of the CVS enzyme were similar to those of liver PC; more than 75% of PC activity was recovered in the mitochondrial fraction of CVS. Apparent Km for pyruvate, ATP, acetyl CoA and HCO3- in the presence of saturation concentrations of the other reactants, were 0.3, 0.44, 0.015 and 6.0 mmol/l, respectively. The optimum pH was 7.5-8.0. The activity of PC in CVS was 3.2 +/- 0.3 nmol/min/mg protein, which is severalfold higher than that of amniotic fluid fibroblasts.     

Health-related quality-of-life assessment of prenatal diagnosis: chorionic villi sampling and amniocentesis

This study assesses the health-related quality-of-life (HRQL) effects of chorionic villi sampling (CVS) and genetic amniocentesis (GA), including both process and outcomes of prenatal diagnosis. The HRQL of 126 women participating in a randomized controlled clinical trial of CVS versus GA in Toronto and Hamilton, Ontario, was assessed in four interviews at weeks 8, 13, 18, and 22 of pregnancy. Statistical analyses included analysis of variance, repeated measures analysis of covariance, chi-square, Fisher's exact test, Student's t-tests, and paired t-tests. Utility scores for patients undergoing CVS exceeded those for GA patients at week 18 (p = 0.04). Utility scores for hypothetical health states did not differ significantly by trial arm. CVS results in slightly improved HRQL during prenatal diagnosis. This advantage needs to be weighed against the high disutility patients attach to infrequent outcomes associated with pregnancy losses, equivocal diagnoses, and diagnostic inaccuracy.     

Transposition of great arteries in an infant born after prenatal diagnosis of trisomy 20 mosaicism

We report a case of prenatally diagnosed mosaic trisomy 20 in cells cultured from amniotic fluid. Trisomy 20 was present in 7 cells (13 percent) in a total of 52 investigated cells. Following the normal findings of an ultrasound scan, the couple decided to continue the pregnancy. A dysmorphic infant was born at the 38 weeks of gestation with generalized dysmorphic features and multiple cardiac anomalies including transposition of great arteries. Chromosome analysis on both cord blood and placenta at birth revealed a normal 46,XX karyotype. This patient is the first case of a liveborn infant with mosaic trisomy 20 cells detected in amniotic fluid culture with transposition of great arteries, atrioventricular concordance and ventricoarterial discordance.     

First-trimester prenatal diagnosis of mucolipidosis II (I-cell disease) by chorionic biopsy

We investigated the possibility of mucolipidosis type II (ML II) prenatal diagnosis by lysosomal enzyme determination on trophoblast biopsy obtained at 10 weeks of gestation in two pregnancies at risk. Diagnosis of ML II was made in both cases on fresh chorionic villi on the basis of depressed beta-galactosidase activity, and after abortion, the diagnosis was confirmed on fresh fetal tissues and on cells cultured from trophoblast and fetuses. We stress the importance of culturing cells from the trophoblast biopsy to ensure a reliable diagnosis.     

Effect of chorionic villus sampling and early pregnancy counselling on uptake of prenatal diagnosis.

An early pregnancy counselling clinic was introduced to improve the uptake of prenatal diagnosis and to offer chorionic villus sampling to women aged 38 and over by their expected date of delivery. Ninety eight (62%) unselected older mothers were seen before 11 weeks'' gestation, and 23 (32%) of those with viable pregnancies elected to undergo chorionic villus sampling compared with 38 (52%) electing amniocentesis. A quarter of the patients booking before 11 weeks had a miscarriage. Because of the future potential demand for chorionic villus sampling counselling during pregnancy and referral of eligible patients should occur as early as possible.     

Accumulated experience with prenatal diagnosis of menkes disease by neutron activation analysis of chorionic villi specimens

Since 1983, prenatal diagnosis of Menkes disease has been carried out by determining Cu in samples of chorionic villi from the fetus by means of radiochemical neutron activation analysis. Concentrations of Cu in chorionic villi from male fetuses later confirmed to have Menkes disease were invariably higher than previously reported values for normal controls. Out of 240 samples analyzed in the period 1983–1998, there were 71 from female fetuses that could be carriers of the Menkes genetic defect without suffering from the disease. Increased concentrations of Cu in these samples could not be attributed to the presence of this genetic defect, but might result from sporadic contamination of the samples before analysis. Such contamination also may occur in samples from male fetuses and thus raise the level of Cu in small, but normal specimens into the range characteristic of Menkes disease. In spite of a strict protocol for taking samples without contamination, a total of four false positives were reported during the period of investigation; no false negatives have occurred.     

Ethical considerations in prenatal diagnosis.

Prenatal diagnostic testing raises a number of important ethical issues, some related to diagnostic testing in general and others related to the special circumstances of pregnancy. These issues are most effectively addressed in the context of a broader understanding of the goals of prenatal diagnosis. Our dual obligations--to the pregnant woman and to the fetus--have an important influence on the goals of testing. Testing seldom leads to treatment beneficial to the fetus, but more often can be beneficial to the pregnant woman, particularly if the information provided enhances her ability to make sound decisions about reproductive matters. The process of prenatal diagnostic testing can, however, limit a woman''s sense of control over the decisions made about her pregnancy. It can also provide an opportunity for third parties to become involved in what are usually considered private matters. It is therefore important that the process of testing include adequate counseling and follow-up and that the patient''s confidence be respected. As prenatal diagnostic technology expands, both in terms of patients to be tested and diagnoses to be sought, society will face difficult questions concerning access to testing and the justification for its use.