Prenatal exclusion of Hurler's disease by leucocyte α-L-iduronidase assay

Hurler's disease was excluded in a fetus at 23 weeks' gestation by demonstrating normal iduronidase activity in fetal leucocytes following failure of amniotic cell culture after amnic-centesis at 16 and 19 weeks' gestation. The diagnosis was confirmed in the neonate.     

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.     

Prenatal diagnosis of DHPR deficiency by direct detection of mutation

Prenatal diagnosis was requested by a family carrying a 3 base-pair insertion in the dihydropteridine reductase (DHPR) coding region. A chorionic villus sample was obtained and fetal DNA was isolated directly from this. Diagnosis was performed by a polymerase chain reaction (PCR)-based technique, with a simple electrophoretic assay for the insertion. The fetus was found to be heterozygous for the insertion. This is the first time that prenatal diagnosis of DHPR deficiency has been performed by direct detection of the mutation.     

Prenatal diagnosis of Fabry's disease by direct analysis of chorionic villi

Six pregnancies of three carriers for X-linked Fabry's disease, were monitored by chromosome and enzyme analysis. Two affected male fetuses were detected by the demonstration of α-galactosidase deficiency in amniotic fluid cells and chorionic villi respectively. The use of chorionic villi enabled a diagnosis within a few hours after sampling in the ninth week of pregnancy whereas the use of amniotic fluid cells in the earlier case required two weeks of culturing after amniocentesis in the 16th week. Four female fetuses were found; heterozygosity was demonstrated in one by analysis of clones in the primary amniotic fluid cell culture.     

Prenatal diagnosis of a fetus harboring an intermediate load of the A3243G mtDNA mutation in a maternal carrier diagnosed with MELAS syndrome

We prenatally diagnosed MELAS syndrome in a fetus whose mother and older brother had the MELAS-specific A3243G mutation. The mutant mtDNA level of the amniotic fluid cells was not significantly different from that of the postnatal peripheral blood and hair follicle samples. The obstetrical course was uncomplicated except for transient exacerbation of the mother's diabetes, which required insulin control. At term, the infant was macrosomic, and the delivery was complicated by shoulder dystocia. MELAS syndrome in itself does not influence either the prenatal course of the mother or the fetal outcome. In contrast to the fulminating clinical course of this mother's first child, MELAS symptoms did not develop in her second child until age four, despite similar high tissue levels of mutant mtDNA. The phenotypic diversity in two offspring with similar higher levels of mutant mtDNA suggests that prenatal genetic diagnosis of cultured amniotic cells may yield results that are poor prognosticators of fetal outcome. Copyright © 2004 John Wiley & Sons, Ltd.     

Prenatal exclusion of late infantile metachromatic leucodystrophy in a late-presenting pregnancy by assay of fetal leucocytes

Metachromatic leucodystrophy was excluded in a fetus at risk, by assay of fetal blood collected at fetoscopy. Isolated fetal leucocytes were shown to have activities of arylsulphatase A and cerebroside sulphatase in the heterozygous range. The prediction was confirmed in the newborn.     

Prenatal exclusion of metachromatic leukodystrophy by estimation of arylsulphatase a activity in chorion and cultured amniotic fluid cells

Chorion biopsy specimens were used for prenatal assay of arylsulphatase A activity in a pregnant woman whose two children had died from metachromatic leukodystrophy (MLD). As in two subsequent pregnancies chorion arylsulphatase A was in the control range, it was concluded that both fetuses were healthy. Absence of MLD in the fetus from the first pregnancy was confirmed after assay of arylsuphatase A activity in fetal organs. The second pregnancy resulted in delivery of a healthy child.     

Prenatal diagnosis of Pelizaeus-Merzbacher disease: detection of proteolipid protein gene duplication by quantitative fluorescent multiplex PCR

A prenatal diagnosis of Pelizaeus-Merzbacher disease (PMD) resulting from proteolipid protein gene (PLP) duplication was performed by a quantitative fluorescent multiplex PCR method. PLP gene copy number was determined in the proband, the pregnant mother, the male fetus and two aunts. Small amounts of genomic DNA extracted from peripheral blood and from chorionic villi were used. The fetus, in common with the proband, was identified as PMD-affected being a carrier of the PLP gene duplication, inherited from the mother, while the two aunts were non-carriers. The data obtained were confirmed by segregation analysis of a PLP-associated dinucleotide-repeat polymorphism amplified by the same multiplex PCR. Copyright © 2001 John Wiley & Sons, Ltd.     

Prenatal detection of free sialic acid storage disease: genetic and biochemical studies in nine families

Sialic acid storage disorders, Salla disease (SD) and a severe infantile form of disease (ISSD), are recessively inherited allelic lysosomal storage disorders due to impaired egress of free sialic acid from lysosomes. Fourteen pregnancies at risk of adult-type free sialic acid storage disease, SD, were monitored by sialic acid assays, genetic linkage or mutation detection analyses using chorionic villus samples. Three affected and 12 unaffected fetuses were identified. The first studies were based on the sialic acid assays alone, but the location of the gene enabled the use of genetic linkage analysis and, more recently, the identification of the SLC17A5 gene and disease-causing mutations added yet another possibility for prenatal studies. A missense mutation 115C→T (R39C) is present in 95% of all Finnish SD alleles, providing an easy and reliable means of diagnostic studies. Both molecular and biochemical (sialic acid assay) studies can be used for prenatal diagnosis of free sialic acid storage diseases. Copyright © 2001 John Wiley & Sons, Ltd.     

Early prenatal direct gene diagnosis of cystic fibrosis in a twin pregnancy and subsequent selective termination

We present a case of prenatal diagnosis of cystic fibrosis (CF) in one twin at 11–12 weeks of gestation. The parents had previously had two children, one of whom is alive and healthy and one who died of CF at the age of 2½ months. The parents were both known to be carriers of the ΔF508 mutation. Chorionic villus sampling (CVS) was performed and direct gene analysis showed that one fetus was homozygous for the ΔF508 mutation, while the other fetus did not have the mutation at all. Both fetuses had normal karyotypes. Selective termination was subsequently performed. The pregnancy continued without complications except for mild pre-eclampsia at term. The woman had a Caesarean section. The genetic diagnosis was confirmed after birth.