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.     

Thermisches Verhalten und hochauflösende Durchstrahlungselektronenmikroskopie von YBa2Cu3O7−x

Dr. Mertin haben wir für seine Hilfe bei der Interpretation der elektronenmikroskopischen Aufnahmen, der Deutschen Forschungsgemeinschaft und dem Fonds der Chemischen Industrie für ihre finanzielle Unterstützung zu danken.     

Activity of biotin-dependent and gaba metabolizing enzymes in chorionic villus samples: Potential for 1st trimester prenatal diagnosis

We have documented the presence of five mitochondrial enzymes in samples of chorionic villus tissue and measured the levels of activity. Three of the enzymes catalyse biotindependent reactions. These are propionyl-CoA carboxylase, 3-methylcrotonyl-CoA carboxylase and pyruvate carboxylase. the other enzymes. 4-aminobutyric acid aminotransferase and succinic semialdehyde dehydrogenase, are involved inthe degradation of the central inhibitory neurotransmitter GABA. Distinct diseases in whichthere is deficiency of each of these enzymes have been documented in man. Significant levels of activity were observed for all five enzymes in chorionic villus tissue. This methodology should permit early prenatal diagnosis of deficiencies of these enzymes by chorionic villus biopsy in the first trimester.     

The cerebro-hepato-renal (Zellweger) syndrome: Prenatal detection based on impaired biosynthesis of plasmalogens

Prenatal diagnosis of the cerebro-hepato-renal (Zellweger) syndrome has been performed in 10 pregnancies at risk by measuring both the activity of acyl CoA: dihydroxyacetonephosphate acyltransferase (DHAP-AT) and the de novo plasmalogen biosynthesis, either in cultured amniotic fluid cells or in fibroblasts cultured from a chorionic villus biopsy. In 7 of the pregnancies both tests indicated no abnormality. All 7 continued to term and normal infants were delivered. However, in amniotic fluid cells from 2 fetuses affected by Zellweger syndrome unequivocal differences from control values were found. The activity of DHAP-AT was clearly deficient and the de novo plasmalogen biosynthesis was impaired. In one pregnancy at risk prenatal diagnosis was performed during the first trimester by measuring both the DHAP-AT activity and the de novo plasmalogen biosynthesis in fibroblasts cultured from a chorionic villi biopsy. From the deficient DHAP-AT activity and the impaired de novo plasmalogen biosynthesis it was concluded that the fetus was affected. This was confirmed biochemically after induced abortion. It can be concluded that measurement of the DHAP-AT activity and the de novo plasmalogen biosynthesis provides convenient methods for the early prenatal detection of Zellweger syndrome.