title: Maternal cell-free DNA-based screening for fetal microdeletion and the importance of careful diagnostic follow-up.
abstract: BACKGROUND
  Noninvasive prenatal screening (NIPS) by next-generation sequencing of cell-free DNA (cfDNA) in maternal plasma is used to screen for common aneuploidies such as trisomy 21 in high risk pregnancies. NIPS can identify fetal genomic microdeletions; however, sensitivity and specificity have not been systematically evaluated. Commercial companies have begun to offer expanded panels including screening for common microdeletion syndromes such as 22q11.2 deletion (DiGeorge syndrome) without reporting the genomic coordinates or whether the deletion is maternal or fetal. Here we describe a phenotypically normal mother and fetus who tested positive for atypical 22q deletion via maternal plasma cfDNA testing.
  
  
  METHODS
  We performed cfDNA sequencing on saved maternal plasma obtained at 11 weeks of gestation from a phenotypically normal woman with a singleton pregnancy whose earlier screening at a commercial laboratory was reported to be positive for a 22q11.2 microdeletion. Fluorescence in situ hybridization and chromosomal microarray diagnostic genetic tests were done postnatally.
  
  
  CONCLUSIONS
  NIPS detected a 22q microdeletion that, upon diagnostic workup, did not include the DiGeorge critical region. Diagnostic prenatal or postnatal testing with chromosomal microarray and appropriate parental studies to determine precise genomic coordinates and inheritance should follow a positive microdeletion NIPS result.
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Svetlana A
authors.initials: SA
authors.lastname: Yatsenko
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: David G
authors.initials: DG
authors.lastname: Peters
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Devereux N
authors.initials: DN
authors.lastname: Saller
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Tianjiao
authors.initials: T
authors.lastname: Chu
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Clemens
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Rajkovic
mesh_terms: D000328:Adult; D002872:Chromosome Deletion; D055028:Comparative Genomic Hybridization; D004247:DNA / Q000097:blood*; D004062:DiGeorge Syndrome / Q000175:diagnosis / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005820:Genetic Testing / Q000379:methods; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods
chemical_list: D004247:DNA