Usefulness of linkage disequilibrium of KM-19 and XV-2c DNA probes for genetic counselling in a high-risk cf family

A French couple with an individual risk of carrying the cystic fibrosis (CF) mutation of 1/2 sought genetic counselling. From the DNA haplotypes generated by XV-2c and KM-19 RFLPs, it could be deduced that only one subject was a carrier, lowering the risk of having a CF baby from 1/16 to 1/200. The strong linkage disequilibrium between these RFLPs and the CF allele observed in France reduced the risk to 1/1600.     

The concurrence of fetal supraventricular tachycardia and obstruction of the foramen ovale

Fetal supraventricular tachycardia (FSVT) is a cardiac arrhythmia that bears a high mortality rate. In the majority of cases no morphological anomalies are found and death is caused by congestive heart failure. This report presents two cases of FSVT in which cross sectional echocardiography revealed obstruction of the foramen ovale with dilatation of the right heart without structural cardiac anomalies. After birth sinus rhythm re-established under digitalis medication in both cases. The association between premature obstruction of the foramen ovale and unexplained intrauterine death in the third trimester of gestation is suggested.     

The psychological effects of false-positive results in prenatal screening for fetal abnormality: A prospective study

The purpose of the study was to describe the impact of false-positive results from initial maternal serum alpha-fetoprotein (MS-AFP) screening. The analyses compared two groups of women, those receiving a negative result (n = 346) and those receiving an initial positive result (n = 26), over four time points—prior to testing, immediately after testing, later in pregnancy, and in the post-partum period. Receiving an abnormal result was associated with high levels of anxiety which were reflected in increased worry about the baby's health and a more negative attitude towards the pregnancy and the baby. Women who had an initial abnormal result were offered a variety of further tests. Those women who went on to have amniocentesis were less worried about their baby's health in the third trimester and also less anxious post-partum than those who did not have amniocentesis. In view of the increasing number of screening tests available, it is necessary to establish whether and how these levels of distress can best be reduced.     

Detection of fetal cells in maternal blood

We report the detection of fetal cells in the maternal circulation by enzymatic amplification of a single copy gene sequence that was fetal-specific. Fetal HLA-A2-positive cells were sorted from maternal HLA-A2-negative cells by flow cytometry and confirmed by demonstration of a fetal-specific HLA-DR4 sequence. However, this sequence could not be detected in unenriched maternal DNA prepared at 28 and 32 weeks' gestation. The sensitivity of detection was 1 HLA-DR4-positive cell in 10⁵ HLA-DR4-negative cells. We conclude that prenatal diagnosis of paternally inherited autosomal-dominant genetic defects may be possible by selective gene amplification of maternal peripheral blood. However, preliminary enrichment for fetal cells may be necessary.     

Prenatal diagnosis of trisomy for the distal two-thirds of the long arm of chromosome 14 (q21→qter)

A de novo case of ‘pure’ trisomy 14q21 → qter is described which was detected at amniocentesis following an abnormal ultrasound scan of a 25–year-old woman. This is apparently the largest distal 14q duplication reported in a case surviving beyond the first trimester. The infant apipeared to have an association of clinical abnormalities previously observed in distal 14q trisomy and proximal 14q trisomy/mosaic trisomy 14.     

Prenatal detection of an Arg→Ter mutation at codon 111 of the pah gene using DNA amplification

A CGA→TGA mutation at codon 111 in exon 3 of the phenylalanine hydroxylase (PAH) gene was recently identified in a Chinese phenylketonuria (PKU) patient. This paper reports the prenatal diagnosis of a Chinese fetus at risk for PKU using DNA amplification with PCR and oligonucleotide hybridization. RFLP analysis revealed that the fetus had inherited a PKU gene from his mother, but his paternal PAH gene was uninformative. PCR amplification of 300 bp which included exon 3 plus the flanking intronic sequences of the PAH gene was performed. The amplified DNA was hybridized with a pair of allele-specific oligonucleotide probes. The results indicated that the fetal DNA carried a PAH 111 Arg→Ter mutant gene inherited from his father. Thus, the fetus was predicted to be affected with PKU.     

Non-immunological hydrops fetalis and intrapericardial teratoma: Case report and review

A large intrapericardial teratoma was found at necropsy in a 38−week stillborn fetus, in which prenatal diagnosis of hydrops fetalis and an ehogenic cardiac mass had been made. Clinical and pathological data are reported. In utero intrapericardial teratomata lead to different outcomes depending on whether fetal hydrops is associated. When generalized fetal hydrops is not present, the outcome is good, even in cases with large pericardial effusions. When generalized fetal hydrops occurs, it often results in a poor outcome. In our literature review, we have found eight perinatal deaths in nine similar cases reported.     

Prenatal diagnosis of pyruvate dehydrogenase E1α subunit deficiency

Pyruvate dehydrogenase (PDH) E1α subunit deficiency is an X-linked inborn error of metabolism affecting males and females with equal frequency. The diagnosis is usually based on determination of enzyme activity, although this may present difficulties in some females because of X-inactivation patterns favouring expression of the normal X chromosome. This is a particular problem for prenatal diagnosis using chorionic villus cells where normal enzyme assay results do not necessarily exclude the diagnosis and confirmatory X-inactivation analysis may be complicated by variable methylation of active and inactive X chromosomes. We describe prenatal diagnosis in two pregnancies in a family following diagnosis of a PDH E1α deficient male. The first prenatal diagnosis was performed by enzyme assay, but by the time of the subsequent pregnancy, the underlying mutation in the affected male had been identified and direct gene analysis was possible. This study highlights the limitations of diagnosis of PDH E1α deficiency based on measurement of the gene product and illustrates the need for mutation analysis in affected individuals.     

Prenatal diagnosis and carrier detection in mucopolysaccharidosis type II by mutation analysis. A 47,xxy male heterozygous for a missense point mutation

Identification of iduronate-2-sulphatase (IDS) gene mutations in patients with mucopolysaccharidosis type II (MPS II, Hunter syndrome) allows fast and reliable carrier detection and prenatal diagnosis. We describe here three cases of prenatal diagnosis by direct detection of the gene mutation. In addition to two affected male fetuses from two different families, a 47,XXY fetus carrying both the normal and the mutant allele was diagnosed in a third family. The latter pregnancy was carried to term and the child is obviously not affected by MPS II.