title: Prevalence of recurrent pathogenic microdeletions and microduplications in over 9500 pregnancies.
abstract: OBJECTIVE
  The implementation of chromosomal microarray analysis (CMA) in prenatal testing for all patients has not achieved a consensus. Technical alternatives such as Prenatal BACs-on-Beads(TM) (PNBoBs(TM) ) have thus been applied. The aim of this study was to provide the frequencies of the submicroscopic defects detectable by PNBoBs(TM) under different prenatal indications.
  
  
  METHODS
  A total of 9648 prenatal samples were prospectively analyzed by karyotyping plus PNBoBs(TM) and classified by prenatal indication. The frequencies of the genomic defects and their 95%CIs were calculated for each indication.
  
  
  RESULTS
  The overall incidence of cryptic imbalances was 0.7%. The majority involved the DiGeorge syndrome critical region (DGS). The additional diagnostic yield of PNBoBs(TM) in the population with a low a priori risk was 1/298. The prevalences of DGS microdeletion and microduplication in the low-risk population were 1/992 and 1/850, respectively.
  
  
  CONCLUSIONS
  The constant a priori risk for common pathogenic cryptic imbalances detected by this technology is estimated to be ~0.3%. A prevalence higher than that previously estimated was found for the 22q11.2 microdeletion. Their frequencies were independent of maternal age. These data have implications for cell-free DNA screening tests design and justify prenatal screening for 22q11 deletion, as early recognition of DGS improves its prognosis.
authors.affiliation: TOMA Advanced Biomedical Assays S.p.A, Busto Arsizio, Italy.
authors.forename: Francesca Romana
authors.initials: FR
authors.lastname: Grati
authors.affiliation: CHI Poissy St Germain, Département de Cytogénétique, Obstétrique et Gynécologie, Poissy, France.
authors.forename: Denise
authors.initials: D
authors.lastname: Molina Gomes
authors.affiliation: 1st Department of Obstetrics and Gynecology, Medical University of Warsaw, Poland.
authors.forename: Jose Carlos Pinto B
authors.initials: JC
authors.lastname: Ferreira
authors.affiliation: Unité de Cytogénétique-Département de Génétique, Hôpital Robert Debré-AP-HP, GHU Nord, Paris, France.
authors.forename: Celine
authors.initials: C
authors.lastname: Dupont
authors.affiliation: Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: Viola
authors.initials: V
authors.lastname: Alesi
authors.affiliation: CHU de Clermont Ferrand, Unit of Cytogenetics, Clermont Ferrand, France.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Gouas
authors.affiliation: United Medix Laboratories Ltd., Department of Genetics, Helsinki, Finland.
authors.forename: Nina
authors.initials: N
authors.lastname: Horelli-Kuitunen
authors.affiliation: Chinese University of Hong Kong, Department of Obstetrics and Gynecology, Hong Kong, China.
authors.forename: Kwong Wai
authors.initials: KW
authors.lastname: Choy
authors.affiliation: iGenomix, PGD Molecular Cytogenetics Lab., Valencia, Spain.
authors.forename: Sandra
authors.initials: S
authors.lastname: García-Herrero
authors.affiliation: CGC Genetics, Laboratory of Cytogenetics, Madrid, Spain.
authors.forename: Alberto Gonzalez
authors.initials: AG
authors.lastname: de la Vega
authors.affiliation: Cytogenetic Unit, Department of Pathology and Genetics, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Piotrowski
authors.affiliation: University 'Federico II', Department of Molecular Medicine and Medical Biotechnology, Naples, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Genesio
authors.affiliation: Hospital General de México Eduardo Liceaga-Facultada de Medicina UNAM, NanoLab, Mexico, Mexico.
authors.forename: Gloria
authors.initials: G
authors.lastname: Queipo
authors.affiliation: TOMA Advanced Biomedical Assays S.p.A, Busto Arsizio, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Malvestiti
authors.affiliation: CHI Poissy St Germain, Département de Cytogénétique, Obstétrique et Gynécologie, Poissy, France.|UPCG, UVSQ, Versaille, France.
authors.forename: Bérénice
authors.initials: B
authors.lastname: Hervé
authors.affiliation: Unité de Cytogénétique-Département de Génétique, Hôpital Robert Debré-AP-HP, GHU Nord, Paris, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Benzacken
authors.affiliation: Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Novelli
authors.affiliation: CHU de Clermont Ferrand, Unit of Cytogenetics, Clermont Ferrand, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Vago
authors.affiliation: United Medix Laboratories Ltd., Department of Genetics, Helsinki, Finland.
authors.forename: Kirsi
authors.initials: K
authors.lastname: Piippo
authors.affiliation: Chinese University of Hong Kong, Department of Obstetrics and Gynecology, Hong Kong, China.
authors.forename: Tak Yeung
authors.initials: TY
authors.lastname: Leung
authors.affiliation: TOMA Advanced Biomedical Assays S.p.A, Busto Arsizio, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Maggi
authors.affiliation: CHI Poissy St Germain, Département de Cytogénétique, Obstétrique et Gynécologie, Poissy, France.
authors.forename: Thibault
authors.initials: T
authors.lastname: Quibel
authors.affiliation: Unité de Cytogénétique-Département de Génétique, Hôpital Robert Debré-AP-HP, GHU Nord, Paris, France.
authors.forename: Anne Claude
authors.initials: AC
authors.lastname: Tabet
authors.affiliation: TOMA Advanced Biomedical Assays S.p.A, Busto Arsizio, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Simoni
authors.affiliation: CHI Poissy St Germain, Département de Cytogénétique, Obstétrique et Gynécologie, Poissy, France.|UPCG, UVSQ, Versaille, France.
authors.forename: François
authors.initials: F
authors.lastname: Vialard
mesh_terms: D000328:Adult; D002872:Chromosome Deletion; D025063:Chromosome Disorders / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics; D058674:Chromosome Duplication; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007621:Karyotyping / Q000379:methods*; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D015995:Prevalence; D012189:Retrospective Studies; D012680:Sensitivity and Specificity