First-trimester diagnosis of an unusual case of α-mannosidosis

Chorionic villi obtained in the first trimester from a pregnancy at risk for α-mannosidosis were shown to have reduced α-mannosidase (EC 3.2.1.24) activity. The pregnancy was terminated and subsequent enzyme studies of the fetal tissues were consistent with the diagnosis of α-mannosidosis. Like the enzyme in the child's fibroblast, α-mannosidase of the chorionic villi from a pregnancy at risk for α-mannosidosis was activated by high substrate concentration and by Zn^{2 +}, and displayed a K_m value two-fold higher than normal. Our results confirm that chorionic villi can be used for early prenatal diagnosis of α-mannosidosis.     

Activities of alkaline phosphatase in first trimester chorion biopsy tissue

We have determined the activity of alkaline phosphatase in chorionic villous tissue obtained in the first trimester of pregnancy, in order to obtain the normal range of values as a prerequisite for application to the prenatal diagnosis of the rare bone disease hypophosphatasia. The activities found were a combination of intestinal and liver/bone/kidney types; traces of placental type were present in only one sample.     

Exclusion of citrullinaemia in the first trimester of pregnancy by direct assay of argininosuccinate synthetase in chorionic villi

Citrullinaemia was presumed to be excluded in a fetus at risk by the direct assay of argininosuccinate synthetase in chorionic villi. The diagnosis was confirmed after amniocentesis by normal argininosuccinate synthetase activity in the cultured amniotic fluid cells and by a normal citrulline concentration in the amniotic fluid. The prediction of a normal fetus was confirmed at term by the birth of a non-citrullinaemic boy.     

Chromosome preparations of both direct and long-term cultures from the same fragment of chorionic villi

A simplified method is described for processing both direct preparations and long-term cultures from the same fragment of chorionic villi. Enzyme separation of the outer trophoblast layers (used for direct preparations) from the inner mesenchymal core (used to initiate long-term cultures) facilitates the utilization of the same fragments for the two procedures, without jeopardizing the success of either method. This has proved useful in cases where the sample was so small that only one method of chromosome preparation may have been possible using other techniques.     

Direct fetal chromosome studies from chorionic villi

An easy and reproducible technique for direct fetal chromosome analysis after chorionic biopsy is described. Very high colchicine concentration and rehydratation of the fixed villi are the two original points of this method.     

Prenatal diagnosis of NADH:ubiquinone oxidoreductase deficiency

NADH:ubiquinone oxidoreductase (complex I of the mitochondrial respiratory chain) deficiency is a severe disorder with an often early fatal outcome. Prenatal diagnosis for complex I defects currently relies mainly on biochemical assays of complex I in fetal tissues such as chorionic villi (CV), and is only in a minority of cases possible by means of mutational analysis of nuclear-encoded genes of complex I. We report on our experience to date with prenatal diagnosis in pregnancies at risk for complex I deficiency. We measured complex I activity in native CV and/or cultured CV in 23 pregnancies in 15 families. In accordance with the results of the investigations in CV, 15 children were born clinically unaffected. Two prenatally diagnosed unaffected fetuses and two prenatally diagnosed affected fetuses were lost prematurely with spontaneous or provoked abortions, respectively. Two affected children were born (prenatally found to be affected). In two pregnancies a discrepancy between native and cultured cells was found. We conclude that prenatal diagnosis for complex I deficiency can be reliably performed. Pitfalls were encountered in using cultured CV as a result of maternal cell contamination (MCC). Future research on pathogenic nuclear mutations underlying complex I deficiency will extend the possibilities for prenatal diagnosis at the molecular level. Copyright © 2001 John Wiley & Sons, Ltd.