Discordant prenatal diagnosis of trisomy 21 due to mosaic structural rearrangements of chromosome 21.
OBJECTIVE
Trisomy 21 mosaicism associated with a structural rearrangement of chromosome 21 is uncommon. We report on two prenatal diagnoses in which karyotypes showed mosaicism with an aberrant cell line, including a structural rearrangement of chromosome 21.


METHODS
Both these cases were associated with increased nuchal translucency. Conventional and molecular cytogenetic analyses were performed on uncultured and cultured trophoblast and amniotic fluid cells.


RESULTS
In Case 1, analysis of trophoblast cells revealed an abnormal karyotype of 47,XX,+mar.ish der(13/21)(D13Z1/D21Z1+)/46,XX. The amniocentesis showed a free non-mosaic trisomy 21. In Case 2, the trophoblast direct analysis showed a normal male karyotype whereas the long-term culture revealed a mosaicism for a dicentric long-arm isochromosome 21: 46,XY,idic(21)(p11)/45,XY,-21/46,XY. Amniocentesis showed an unbalanced non-mosaic karyotype 46,XY,idic(21)(p11) resulting therefore in trisomy for the long arm of chromosome 21.


CONCLUSIONS
Our cases underline the importance of combining the direct analysis and long-term culture of trophoblast and emphasise the need for confirmatory studies in other tissues when mosaicism of structural rearrangement is encountered in chorionic villi. The meiotic and mitotic mechanisms of formation of these structural rearrangements of chromosome 21 are discussed.
Brisset
Sophie
S
Service de Génétique et Reproduction, AP-HP, Hôpital Antoine Béclère, Clamart, France. sophie.brisset@abc.ap-hop-paris.fr
Aboura
Azzedine
A
Audibert
François
F
Costa
Jean-Marc
JM
L'Herminé
Aurore Coulomb
AC
Gautier
Valérie
V
Frydman
René
R
Tachdjian
Gérard
G
D000328:Adult; D000649:Amniocentesis; D000653:Amniotic Fluid / Q000166:cytology; D002478:Cells, Cultured; D015193:Chorionic Villi Sampling; D002869:Chromosome Aberrations; D002891:Chromosomes, Human, Pair 21; D004247:DNA / Q000097:blood; D004314:Down Syndrome / Q000175:diagnosis*; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008297:Male; D009030:Mosaicism; D009333:Neck / Q000000981:diagnostic imaging / Q000196:embryology; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D015203:Reproducibility of Results; D014463:Ultrasonography
D005819:Genetic Markers; D004247:DNA