An audit of trisomy 16 in man

Sufficient information is now available from the literature to produce an audit of trisomy 16, in a theoretical cohort of 100 000 recognized pregnancies, from gametogenesis to term and onwards. Recent reports of premature separation of chromosome 16 bivalents during maternal meiosis I provide a novel mechanism for generation of this aneuploidy. Most, if not all, errors resulting in recognized mosaic and non-mosaic trisomy 16 pregnancies investigated using polymorphic DNA markers appear to originate at that stage. The incidence of this maternally derived trisomy 16 in the late first trimester is equivalent to 1500 cases in 100 000 recognized pregnancies, a figure which now corresponds very closely to the reinterpreted oogenesis data. Most trisomy 16 pregnancies are lost around 12 weeks' gestation, but of the order of 10 per cent (120–150 in this audit) undergo reduction to disomy, with 30 of these excluding aneuploidy from the fetal cell lineage (trisomic zygote rescue) and continuing into the second trimester. Maternal uniparental disomy (UPD) in one-third of this latter group is associated with loss later in pregnancy or severe intrauterine growth retardation, but can be compatible with a viable pregnancy. Adverse pregnancy outcomes are not restricted to those with UPD. Analysis of reports of confined placental mosaicism for chromosome 16 without associated UPD indicates that the presence of high levels of trisomic cells in the placenta alone consistently produces a more variable inhibition of fetal growth, which may also, in cases, be associated with late pregnancy loss.     

Maternal uniparental heterodisomy for chromosome 2: detection through ‘atypical’ maternal AFP/hCG levels,with an update on a previous case

We report a case of maternal uniparental disomy 2, detected through routine screening of placental karyotypes following the finding of ‘atypical’ AFP/hCG levels in the second trimester, with intrauterine growth retardation (IUGR) but otherwise normal outcome at term. Although the child remained small, subsequent early physical and mental development has also been normal. Additionally, we report long-term follow-up of an earlier case, again with relatively normal physical and mental development. The significance of atypical AFP/hCG results and the predictive value of prenatal testing for UPD2 in trisomy 2 confined placental mosaicism (CPM) cases are discussed. Copyright © 2001 John Wiley & Sons, Ltd.     

A case of paternal uniparental disomy for chromosome 11

We report a case of paternal uniparental disomy for chromosome 11 that presented as severe intrauterine growth retardation. Autopsy following intrauterine death also revealed aberrant intestinal rotation and hypospadias. Chromosome analysis of direct preparations from placental biopsy showed an abnormal 47,XY,+11 karyotype. Analysis of long-term cultures from the placenta revealed 46,XY/47,XY,+11 mosaicism. Fluorescence in situ hybridization (FISH) studies on interphase nuclei confirmed trisomy 11 in multiple placental sites but detected only disomic cells in fetal skin. Investigation using microsatellite polymorphisms demonstrated paternal isodisomy at loci D11S909, D11S956, and D11S488, and paternal heterodisomy at locus D11S928.     

Prenatal detection of multiple copies of a familial supernumerary marker chromosome

Direct preparations and long-term cultures from a chorion villus biopsy, taken because of a known maternal additional marker chromosome, showed a 48,XX,+mar,+mar karyotype in all cells examined. The same karyotype was revealed in a subsequent amniotic fluid sample and in cord blood at delivery. Detailed examination of the child at delivery and at 1 year of age showed no evidence of phenotypic abnormality or developmental problems.     

Amylo-1,6-glucosidase activity in cultured cells: A deficiency in type III glycogenosis with prenatal studies

Deficiency of amylo-1,6–glucosidase activity was expressed in parallel in liver and skin fibroblasts from a patient with type III glycogenosis. In crude extracts of control liver and muscle, amylo-1, 6–glucosidase (M.W. 164000) was identified by immunoprecipitation; no cross-reacting material was found in the patient's liver. Assay of amylo-1,6–glucosidase activity in cultured skin fibroblasts from the affected family revealed less than 10 per cent of control value in mutant homozygous cells whereas in cells from the parents, activity was reduced to 40–60 per cent of the control value. Activity in cultured amniotic fluid cells was similar to that of control fibroblasts. In cultured amniotic fluid cells obtained during the mother's subsequent pregnancy, the normal amylo–1,6–glucosidase activity measured, predicted correctly the outcome of this pregnancy prior to the 20th week of gestation.     

Practical experience using transabdominal chorionic villus biopsies taken after 16 weeks' gestation for rapid prenatal diagnosis of chromosomal abnormalities

Placental biopsy was performed on 81 patients at greater than 16 weeks' gestation. The major indication for such biopsies was an increased risk of chromosomal abnormality because of either abnormal ultrasound findings or late presentations for advanced maternal age. Six abnormal karyotypes resulting in elective termination were found. The use of rapid karyotyping by this procedure as an alternative to amniocentesis or fetal blood sampling is discussed.