title: A French Approach to Test Fetuses with Ultrasound Abnormalities Using a Customized Microarray as First-Tier Genetic Test.
abstract: Cytogenetic microarray analysis is now the first-tier genetic test used in a postnatal clinical setting to explore genomic imbalances in individuals with developmental disability and/or birth defects. However, in a prenatal setting, this technique is not widely implemented, largely because the clinical impact of some copy number variants (CNVs) remains difficult to assess. This limitation is especially true in France where termination of pregnancy for medical reasons may be performed at any stage of gestation. During a period of 15 months, we investigated 382 fetuses presenting with ultrasound anomalies, using a customized microarray designed to avoid the detection of CNVs raising challenges for genetic counseling. After excluding common aneuploidies, 20/374 (5.3%) fetuses had a pathogenic CNV, among which 12/374 (3.2%) could have been detected by karyotyping, whereas 8/374 (2.1%) were cryptic. Within these 374 cases, 300 were ongoing pregnancies at the time of array comparative genomic hybridization (aCGH) testing. For these pregnancies, we detected 18/300 (6%) pathogenic CNVs, among which 6/300 (2%) were cryptic. Using this approach, only 2/300 (0.6%) of the detected CNVs raised difficulties for genetic counseling. This study confirms the added value of this strategy in a prenatal clinical setting to minimize ethical issues for genetic counseling while enhancing the detection of genomic imbalances.
authors.affiliation: Service d'Histologie-Embryologie-Cytogx00E9;nx00E9;tique, Hx00F4;pital Necker-Enfants Malades, AP-HP, Paris, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Malan
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Lapierre
authors.forename: Matthieu
authors.initials: M
authors.lastname: Egloff
authors.forename: Didier
authors.initials: D
authors.lastname: Goidin
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Beaujard
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Maurin
authors.forename: Tania
authors.initials: T
authors.lastname: Attié-Bitach
authors.forename: Bettina
authors.initials: B
authors.lastname: Bessières
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bernard
authors.forename: Philippe
authors.initials: P
authors.lastname: Roth
authors.forename: Julien
authors.initials: J
authors.lastname: Stirnemann
authors.forename: Laurent
authors.initials: L
authors.lastname: Salomon
authors.forename: Serge
authors.initials: S
authors.lastname: Romana
authors.forename: Michel
authors.initials: M
authors.lastname: Vekemans
authors.forename: Yves
authors.initials: Y
authors.lastname: Ville
authors.forename: Catherine
authors.initials: C
authors.lastname: Turleau
mesh_terms: D002869:Chromosome Aberrations / Q000196:embryology; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000235:genetics; D005333:Fetus / Q000378:metabolism*; D005602:France; D005817:Genetic Counseling; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D007621:Karyotyping; D046228:Microarray Analysis / Q000379:methods*; D011247:Pregnancy; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016216:Ultrasonography, Prenatal / Q000379:methods*