Prenatal diagnosis of spinal muscular atrophy in Russia

Ninety-two families with spinal muscular atrophy (SMA) applied for genetic counselling and further prenatal diagnosis. To minimize expenses, only one tightly linked informative marker was determined in the course of preliminary examination, and non-radioactive allele detection was preferably used. Four prenatal diagnoses of SMA type I, four of SMA type II, and one of SMA type III were made. This trial programme shows the considerable requirements, importance, and potential effectiveness of prenatal prediction of SMA in Russia.     

Human parvovirus B19 infection and unbalanced translocation in a case of hydrops fetalis

In a case of hydrops fetalis, serological examination showed a recent maternal human parvovirus B19 infection. Amniocentesis revealed a unique unbalanced translocation between chromosomes 3 and 11 of the fetus. The mother proved to have a balanced reciprocal translocation between chromosomes 3 and 11. A grossly macerated hydropic male fetus was delivered with a flat nose and low implanted deformed ears. Histopathological examination revealed nuclear inclusion bodies in fetal erythroid cells, confirming human parvovirus B19 infection. Parvovirus B19 DNA was demonstrated by in situ hybridization in the nuclei of heart muscle cells. Our finding of two different disorders in one case illustrates the importance of a complete evaluation of every case of hydrops fetalis, especially concerning counselling on the outcome of future pregnancies. The human parvovirus B19 infection will not recur due to the acquired immunity of the mother, whereas the balanced reciprocal translocation will endanger future pregnancies.     

Verification of carrier status for Becker muscular dystrophy from analysis of a blighted ovum

The polymerase chain reaction (PCR) was used on material from a blighted ovum to confirm indirectly the carrier status of a woman with a family history of Becker muscular dystrophy. Conventional testing including creatine kinase levels, muscle biopsy, and EMG had been inconclusive, and on the basis of one elevated creatine kinase level, the woman had been designated a possible carrier. Ultrasound examination at 10 weeks of pregnancy indicated a blighted ovum, from which DNA was subsequently extracted and subjected to PCR testing for determination of sex and genotypic status with respect to the known familial deletion of the dystrophin gene. The blighted ovum was found to have a Y chromosome and also to be deleted for at least exon 6 of the dystrophin gene, indirectly indicating that the mother most likely carried the family mutation for Becker muscular dystrophy.     

Prenatal diagnosis of Freeman–Sheldon syndrome (whistling face)

The diagnosis of Freeman–Sheldon syndrome was made by ultrasonographic evaluation of a 20-week fetus with a positive family history. The ultrasonographic features were abnormalities of the extremities and mouth.     

Detection of low-grade mosaicism in fetal cells isolated from maternal blood

Recovering and analysing fetal erythrocytes from maternal blood is being pursued for non-invasive prenatal genetic diagnosis. We report the observation of 46, XY/47, XXY mosaicism in fetal cells from a woman whose first-trimester chorionic villus sampling (CVS) initially showed only 46, XY. Only after exhaustive (500 cells) analysis were four XXY cells found in cultured villi.     

Pitfalls in the prenatal diagnosis of peroxisomal β-oxidation defects by chorionic villus sampling

Variability in the level of expression of very long chain fatty acids (VLCFAs) is documented in cultured chorionic villus (CV) cells derived from two fetuses, one at risk for an unusual peroxisomal fatty acid β-oxidation defect, and the other at risk for the X-linked form of adrenoleucodystrophy (ALD). Cells from early subcultures of chorionic cells from both cases gave normal values for VLCFA ratios. The results for the fetus at risk for the β-oxidation defect were interpreted to indicate that the fetus was not affected; however, at birth, the infant was clinically and biochemically affected. In the case of the fetus at risk for X-linked ALD, although VLCFAs were normal in subculture 1, the levels of these fatty acids increased dramatically in subculture 3, suggesting an abnormal fetus. Termination of the pregnancy and subsequent biochemical and morphological follow-up confirmed that the fetus was indeed affected by ALD.     

Extraction of DNA from amniotic fluid cells for the early prenatal diagnosis of genetic disease

Ten-ml samples of amniotic fluid were taken from pregnancies being terminated at 8–14 weeks' gestation. DNA was extracted from the amniotic cells by sequential centrifugation and analysed using the polymerase chain reaction (PCR). Fifteen samples were analysed for evidence of maternal contamination using Mfd5 oligo-nucleotide primers for repeat polymorphisms. Ten amniotic fluid samples were tested for the Delta-F₅₀₈ deletion characteristic of cystic fibrosis to demonstrate a diagnostic application for the technique. In each case, DNA extracted from fetal tissue from the same pregnancy was included in the controls. In 14 of the 15 cases tested with the Mfd5 primers, both the amniotic fluid DNA and the fetal DNA showed no evidence of contaminating DNA. In one case, neither the amniotic fluid cells nor the fetal cells yielded results. In nine of the ten cases tested with the Delta-F₅₀₈ primers, the amniotic fluid cell DNA provided accurate information about the genetic status of the fetus; in the tenth, the fetal DNA failed to amplify. The results indicate that adequate DNA can be extracted from amniotic fluid from 8 weeks' gestation onward and these samples are suitable for prenatal diagnosis using PCR.     

Prenatal screening and diagnosis of neural tube defects in England and Wales in 1985

A survey was carried out to determine the effect of prenatal screening and therapeutic abortion on births in 1985 with anencephaly and spina bifida in England and Wales. Maternal serum alpha-fetoprotein tests were done on 399 288 women (60 per cent of pregnant women): 4 per cent were reported as being screen-positive and 1 per cent had an amniocentesis. An estimated 534 pregnancies associated with anencephaly were terminated and an estimated 445 pregnancies associated with spina bifida (but without anencephaly) were terminated. Most (63 per cent) of the anencephalic pregnancies were first suspected from an ultrasound examination; 57 per cent of the spina bifida pregnancies were first suspected from a positive maternal serum alpha-fetoprotein test, 35 per cent by ultrasound, and the remaining 8 per cent by other means. The birth prevalence of anencephaly declined by 94 per cent between 1964–1972 and 1985, but when the terminations of pregnancy on account of having a fetus with anencephaly are added to the births the decline in prevalence was only 50 per cent. The birth prevalence of spina bifida declined by 68 per cent over the same period but when the terminations were added to the births the decline in prevalence was only 32 per cent. Among births with anencephaly 66 per cent had had no screening or diagnostic tests in early pregnancy, but in those that did nearly all were positive–usually in twin pregnancies where one fetus was affected but not the other. Among births with spina bifida, 48 per cent had no tests and in those that did the results were mainly negative. We conclude that in order to monitor adequately the national screening programme for anencephaly and spina bifida a special neural tube defects register should be formed.