A retrospective study by oligonucleotide array-CGH analysis in 50 fetuses with multiple malformations.
OBJECTIVE
To retrospectively define the frequency and the nature of submicroscopic chromosomal imbalances among fetuses with multiple congenital anomalies (MCA).


METHODS
We used oligonucleotide arrays to perform comparative genomic hybridization after termination of pregnancy in 50 polymalformated fetuses with a normal karyotype. These fetuses presented with at least three significant malformations (42 cases) or a severe brain anomaly (eight cases).


RESULTS
We identified a deleterious copy number variation (CNV) in five fetuses (10%). De novo genomic imbalances identified in this study consisted of a 6qter deletion in a fetus with brain and renal malformations, a mosaicism for a 8p tetrasomy in a fetus with agenesis of corpus callosum, growth retardation, mild facial dysmorphic features, and vertebral anomalies, a 17p13.3 deletion in a fetus with a complex brain malformation, and a partial 11p trisomy in a fetus with severe growth retardation and oligoamnios. In one case, we identified a partial 17q trisomy resulting from malsegregation of a cryptic-balanced translocation.


CONCLUSIONS
This study shows that array comparative genomic hybridization (aCGH) is particularly effective for identifying the molecular basis of the disease phenotype in fetuses with multiple anomalies. Our study should help to define clinical relevant regions that would need to be included in targeted arrays designed for prenatal testing.
Valduga
M
M
Laboratoire de Génétique Médicale, Nancy Université, Centre Hospitalier Régional et Universitaire, Rue du Morvan, Vandoeuvre-les-Nancy cedex 1, France. m.valduga@chu-nancy.fr
Philippe
C
C
Bach Segura
P
P
Thiebaugeorges
O
O
Miton
A
A
Beri
M
M
Bonnet
C
C
Nemos
C
C
Foliguet
B
B
Jonveaux
P
P
D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D000328:Adult; D055028:Comparative Genomic Hybridization; D005260:Female; D005333:Fetus / Q000473:pathology; D018628:Gene Dosage; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy; D012189:Retrospective Studies