First‐trimester biochemical and molecular diagnoses using chorionic villi: High accuracy in the U.S. collaborative study

R. J. Desnick, J. L. Schuette, M. S. Golbus, L. Jackson, H. A. Lubs, D. H. Ledbetter, M. J. Mahoney, E. Pergament, J. L. Simpson, J. M. Zachary, S. E. Fowler, G. G. Rhoads, F. De La Cruz

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


The accuracy of biochemical and molecular prenatal diagnoses using chorionic villi as the fetal source was assessed by seven centres participating in the NICHD collaborative study on the safety and accuracy of chorionic villus sampling (CVS) and amniocentesis. Of 601 pregnancies studied, biochemical methods were used to determine the diagnosis in 283 fetuses at risk for 35 different metabolic disorders. Fifteen different lysosomal storage diseases accounted for 81 per cent of the biochemical prenatal diagnoses performed, with 57 per cent of these pregnancies at risk for Tay‐Sachs disease. No errors were made in the biochemical diagnoses that predicted affected or unaffected fetuses. However, the diagnoses of certain disorders (e.g., mucopolysacchariodosis type IH, metachromatic leukodystrophy, and Krabbe disease) occasionally required confirmatory studies in cultured amniocytes because the enzyme results were inconclusive in direct and/or cultured villi or due to the presence of a pseudodeficiency allele. Of these, only the diagnosis of a fetus at risk for Krabbe disease remained inconclusive after special studies to discriminate between mutant and pseudodeficiency alleles. Recombinant DNA techniques were used to predict the diagnosis of 318 fetuses at risk for 16 different disorders in which the defective disease gene could be detected either directly or by linkage analysis to a nearby polymorphic marker. Of these, 32 per cent were for haemoglobinopathies, 25 per cent for cystic fibrosis, 24 per cent for Duchenne or Becker muscular dystrophy, and 7 per cent for haemophilias. Pregnancies at risk for known disorders with specific molecular lesions (e.g., sickle cell disease) were accurately diagnosed in direct and/or cultured villi. Diagnoses requiring analyses with closely linked polymorphic markers were occasionally uninformative or inconclusive. Maternal contamination was not reported in any biochemical or molecular‐based diagnosis. These studies document the high accuracy and rapidity of both biochemical and mutation‐specific prenatal diagnoses with direct and cultured chorionic villi.

Original languageEnglish (US)
Pages (from-to)357-372
Number of pages16
JournalPrenatal Diagnosis
Issue number5
StatePublished - May 1992

All Science Journal Classification (ASJC) codes

  • Obstetrics and Gynecology
  • Genetics(clinical)


  • Chorionic villus sampling
  • Enzymes
  • Inherited metabolic disease
  • Linkage analysis
  • Molecular diagnostics
  • Prenatal diagnosis


Dive into the research topics of 'First‐trimester biochemical and molecular diagnoses using chorionic villi: High accuracy in the U.S. collaborative study'. Together they form a unique fingerprint.

Cite this