Use of the chemical cleavage of mismatch method for prenatal deficiency diagnosis of alpha-1-antitrypsin

The most common mutation in alpha-1-antitrypsin deficiency, conversion of a G to an A at base 9989 (PI-Z), was detected with the chemical cleavage of mismatch method, demonstrating the power of the method for prenatal diagnosis. Exon V of the gene was amplified using the polymerase chain reaction and heteroduplexes were formed to test for the presence of the mutation. The predicted C mismatch was readily detectable with hydroxylamine, and by making the probe from the chorionic villus sample it was possible to determine that the fetus was heterozygous, not homozygous, for the mutation.     

Maternal Serum CA 125 for aneuploidy detection in early pregnancy

Maternal serum CA 125 levels were determined at 9–11 menstrual weeks for 26 cases of trisomy 13 (n = 4), trisomy 18 (n = 7), trisomy 21 (n = 15), and appropriate controls. There were no statistically significant differences between groups.     

Reproductive behaviour and prenatal diagnosis following genetic termination of pregnancy in women of advanced maternal age

One hundred and fifty-one women of advanced maternal age who underwent genetic termination of pregnancy (TOP) were studied for their reproductive behaviour and the type of procedure for prenatal diagnosis in a subsequent pregnancy. A total of 59 women (39 per cent) had a further pregnancy. In all continuing pregnancies prenatal diagnosis was performed, of which 75 per cent consisted of chorionic villus sampling (CVS). Reproductive behaviour following a genetic termination was negatively correlated with maternal age and parity. Both reproductive behaviour and the choice to undergo a diagnostic procedure in the next pregnancy were independent of the type of diagnostic procedure in the previous affected pregnancy.     

Parental response to mid-trimester therapeutic abortion following amniocentesis

This article reports the results of a retrospective study designed to examine the responses of couples to genetic amniocentesis and subsequent therapeutic abortions due to birth defects. Fourteen women and 12 men were interviewed by experienced interviewers using a structured format designed by the authors, and each interview was audiotaped for later rating. The 5 raters (all women) were instructed to independently rate each interview using forms designed by the authors to elicit information about many aspects of the participant's individual responses as well as perceptions of spouse's responses to the process of pregnancy, amniocentesis, therapeutic abortion, and sequelae. Ratings of all 5 raters were conjoined and an homogeneous narrative was constructed for each interview. Results indicate, in general, that the respondent couples coped well with this experience. In fact 70 per cent of the respondent couples described their marital relationships as becoming closer as a result of their experience. Only a few participants reported long-term deleterious effects. Most couples coped by relying on relatives, friends, and occasionally, professional counsellors. In addition, most participants in this study suggested ways to improve the medical and psychological aspects of this experience.     

Adult-onset GM2 gangliosidosis diagnosed in a fetus

Amniocentesis and subsequent tests are reported on a fetus conceived of a rare mating type: its mother has an intermediate level of β hexosaminidase A (HEX A), characteristic of carriers of Tay-Sachs disease (TSD), while the father suffers from an adult-onset GM₂ ganglio-sidosis (AOG) with severe HEX A deficiency. Activity of HEX A in the cultured fetal cells was very low when measured by the heat-inactivation method, thus showing the typical biochemical phenotype of TSD fetuses. However, upon separation of HEX isozymes by ion exchange chromatography, residual HEX A (17 per cent of total HEX) was demonstrated. Also in contrast to TSD fetuses, this fetus' fibroblasts were able to synthesize the precursor of a chains of HEX, and ultrastructural examination of its brain revealed few atypical lamellar bodies, unlike those found in TSD fetuses of the same gestational age. It is therefore concluded that the fetus was not affected with TSD, but rather with AOG.     

Ionic liquids as lubricants or lubrication additives: An ecotoxicity and biodegradability assessment

This paper reports on the (eco)toxicity and biodegradability of ionic liquids considered for application as lubricants or lubrication additives. Ammonium- and pyrrolidinium-based cations combined with methylsulphate, methylsulphonate and/or (CF₃SO₂)₂N⁻ anions were investigated in tests to determine their aquatic toxicity using water fleas Daphnia magna, green algae Selenastrum capricornutum and marine bacteria (Vibrio fischeri). Additional test systems with an isolated enzyme (acetylcholinesterase) and isolated leukaemia cells from rats (IPC-81) were used to assess the biological activity of the ionic liquids. These compounds generally exhibit low acute toxicity and biological activity. Their biodegradability was screened according to OECD test procedures 301 B and 301 F. For choline and methoxy-choline ionic liquids ready biodegradability was observed within 5 or 10 d, respectively. Some of the compounds selected have a considerable potential to contribute to the development of more sustainable products and processes.     

Prenatal diagnosis of inborn errors in peroxisomal β-oxidation

In recent years, an increasing number of inherited diseases in man have been recognized in which there is an impairment in the peroxisomal β-oxidation of very-long-chain fatty acids. In general, these disorders are associated with severe neurological and physical abnormalities and death within the first years of life. In this paper we describe our experience with regard to the prenatal diagnosis of a number of different inborn errors of peroxisomal β-oxidation. Eleven pregnancies at risk were monitored by measuring very-long-chain fatty acid levels as well as very-long-chain fatty acid β-oxidation in cultured chorionic villous fibroblasts and/or amniotic fluid cells. Five affected fetuses were identified. It is concluded that prenatal diagnosis in this group of diseases can be done reliably using cultured chorionic villous fibroblasts or amniotic fluid cells.     

Early amniocentesis at 11–14 weeks' gestation for the diagnosis of fetal chromosomal abnormality—a clinical evaluation

Early arnniocentesis between 11 and 14 weeks' gestation was offered to 110 women at risk of a chromosomally abnormal fetus due to maternal age. Four were found to be unsuitable for the procedure, and 106 early amniocenteses were performed. In 102 cases, clear amniotic fluid was obtained with a single tap. There were two dry taps and two bloodstained tapis; sampling was repeated in three of these cases before 15 weeks. In the fourth case, placental biopsy was performed at 16 weeks. Thus, we were able to obtain a satisfactory sample in all but three cases(2.8 percent). Karyotyping of cells harvested from the early amniotic fluid samples was successful in all the 105 cases. Cell culture from the initial samples revealed a normal karyotype in 99 cases, two balanced translocations, two tetraploid karyotypes, and two cases of pseudomosaicism. Of the 105 pregnancies successfully sampled, there have been two losses to date (1–8 per cent). Two further patients presented with premature rupture of membranes, both pregnancies having successful outcomes. Sixty-two babies have delivered to date, with four congenital anomalies. There were no respiratory problems. Twenty-nine pregnancies are continuing without known complications, and details are not yet available on the remaining 12. The results indicate that early arnniocentesis may replace the traditional test at 15–17 weeks.     

Pallister-Killian syndrome diagnosed by chorionic villus sampling

The first prenatal diagnosis of Pallister-Killian syndrome by chorionic villus sampling is presented. Fetal hydrops was noted on ultrasound in early pregnancy, and the karyotype revealed isochromosome 12p mosaicism.