title: Exome sequencing positively identified relevant alterations in more than half of cases with an indication of prenatal ultrasound anomalies.
abstract: OBJECTIVE
  Exome sequencing is a successful option for diagnosing individuals with previously uncharacterized genetic conditions, however little has been reported regarding its utility in a prenatal setting. The goal of this study is to describe the results from a cohort of fetuses for which exome sequencing was performed.
  
  
  METHODS
  We performed a retrospective analysis of the first seven cases referred to our laboratory for exome sequencing following fetal demise or termination of pregnancy. All seven pregnancies had multiple congenital anomalies identified by level II ultrasound. Exome sequencing was performed on trios using cultured amniocytes or products of conception from the affected fetuses.
  
  
  RESULTS
  Relevant alterations were identified in more than half of the cases (4/7). Three of the four were categorized as 'positive' results, and one of the four was categorized as a 'likely positive' result. The provided diagnoses included osteogenesis imperfecta II (COL1A2), glycogen storage disease IV (GBE1), oral-facial-digital syndrome 1 (OFD1), and RAPSN-associated fetal akinesia deformation sequence.
  
  
  CONCLUSIONS
  This data suggests that exome sequencing is likely to be a valuable diagnostic testing option for pregnancies with multiple congenital anomalies detected by prenatal ultrasound; however, additional studies with larger cohorts of affected pregnancies are necessary to confirm these findings.
authors.affiliation: Ambry Genetics, Aliso Viejo, CA, USA.
authors.forename: Christina L
authors.initials: CL
authors.lastname: Alamillo
authors.affiliation: Ambry Genetics, Aliso Viejo, CA, USA.
authors.forename: Zöe
authors.initials: Z
authors.lastname: Powis
authors.affiliation: Ambry Genetics, Aliso Viejo, CA, USA.
authors.forename: Kelly
authors.initials: K
authors.lastname: Farwell
authors.affiliation: Ambry Genetics, Aliso Viejo, CA, USA.
authors.forename: Layla
authors.initials: L
authors.lastname: Shahmirzadi
authors.affiliation: Ambry Genetics, Aliso Viejo, CA, USA.
authors.forename: Elaine C
authors.initials: EC
authors.lastname: Weltmer
authors.affiliation: Genetics Department, Kaiser Permanente, Clovis, CA, USA.
authors.forename: John
authors.initials: J
authors.lastname: Turocy
authors.affiliation: Thomas Lowe, MD, Private Practice, Boca Raton, FL, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lowe
authors.affiliation: Genetics Department, Kaiser Permanente, San Francisco, CA, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Kobelka
authors.affiliation: Genetics Department, Kaiser Permanente, San Francisco, CA, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Chen
authors.affiliation: Division of Genetics, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Donald
authors.initials: D
authors.lastname: Basel
authors.affiliation: Division of Maternal-Fetal Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Ashkinadze
authors.affiliation: Integrated Genetics, Westborough, MA, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: D'Augelli
authors.affiliation: Ambry Genetics, Aliso Viejo, CA, USA.|Department of Pediatrics, University of California Irvine, Irvine, CA, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Chao
authors.affiliation: Ambry Genetics, Aliso Viejo, CA, USA.
authors.forename: Sha
authors.initials: S
authors.lastname: Tang
mesh_terms: D000015:Abnormalities, Multiple / Q000000981:diagnostic imaging / Q000235:genetics*; D000028:Abortion, Induced; D001176:Arthrogryposis / Q000000981:diagnostic imaging / Q000235:genetics; D024042:Collagen Type I / Q000235:genetics; D000013:Congenital Abnormalities / Q000000981:diagnostic imaging / Q000235:genetics*; D059472:Exome / Q000235:genetics*; D005260:Female; D005313:Fetal Death; D005820:Genetic Testing; D006004:Glycogen Debranching Enzyme System / Q000235:genetics; D006011:Glycogen Storage Disease Type IV / Q000000981:diagnostic imaging / Q000235:genetics; D006801:Humans; D008297:Male; D009154:Mutation; D009958:Orofaciodigital Syndromes / Q000000981:diagnostic imaging / Q000235:genetics; D010013:Osteogenesis Imperfecta / Q000000981:diagnostic imaging / Q000235:genetics*; D011247:Pregnancy; D011506:Proteins / Q000235:genetics; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA; D016216:Ultrasonography, Prenatal
chemical_list: C000601279:COL1A2 protein, human; D024042:Collagen Type I; D006004:Glycogen Debranching Enzyme System; C115130:OFD1 protein, human; D011506:Proteins; C577876:GBE1 protein, human