Array CGH analysis in high-risk pregnancies: comparing DNA from cultured cells and cell-free fetal DNA.
OBJECTIVE
To compare results of array comparative genomic hybridization (CGH) on cell-free fetal (cff) DNA from amniotic fluid supernatant and DNA from cultured amniocytes in high-risk pregnancies.


METHODS
We selected 48 cases of high-risk pregnancies (in utero growth retardation [IUGR] and/or at least two fetal malformations [polymalformation]). Bacterial artificial chromosome array CGH (BlueGnome) was performed on 38 fetal samples (frozen cff DNA and DNA from cultured cells) with previously normal karyotypes.


RESULTS
From the 38 specimens, we obtained an adequate amount of sufficient quality DNA with a better quality profile using cff DNA compared to cellular DNA. Aberrations of clinical relevance were detected in three fetuses, and copy number variations considered as benign polymorphism were detected in one case using both sources of DNA. This results in an 8% detection rate of significant abnormalities in high-risk pregnancies with a normal karyotype using array CGH (two cases with IUGR, one with polymalformation).


CONCLUSIONS
These findings indicate the possibility of using cff DNA from amniotic fluid supernatant for array CGH with excellent results, even in late pregnancy when culture is no longer available. In this small series, pathogenic copy number variations are detected more often in the presence of IUGR than with polymalformation.
Laboratoire de Cytogénétique Prénatale, Service de Génétique, CHU Caen Côte de Nacre, UFR de Médecine Caen, Caen, France. gruchy-n@chu-caen.fr
Nicolas
N
Gruchy
Matthieu
M
Decamp
Nicolas
N
Richard
Corinne
C
Jeanne-Pasquier
Guillaume
G
Benoist
Hervé
H
Mittre
Nathalie
N
Leporrier
D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics*; D000328:Adult; D000649:Amniocentesis / Q000379:methods*; D000653:Amniotic Fluid / Q000737:chemistry / Q000166:cytology; D002478:Cells, Cultured; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D055028:Comparative Genomic Hybridization / Q000379:methods*; D004247:DNA / Q000097:blood; D056915:DNA Copy Number Variations; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D005317:Fetal Growth Retardation / Q000175:diagnosis / Q000235:genetics*; D005865:Gestational Age; D006801:Humans; D059785:Karyotype; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy; D012189:Retrospective Studies
D004247:DNA