title: Identification of copy number variations associated with congenital heart disease by chromosomal microarray analysis and next-generation sequencing.
abstract: OBJECTIVE
  To determine the type and frequency of pathogenic chromosomal abnormalities in fetuses diagnosed with congenital heart disease (CHD) using chromosomal microarray analysis (CMA) and validate next-generation sequencing as an alternative diagnostic method.
  
  
  METHODS
  Chromosomal aneuploidies and submicroscopic copy number variations (CNVs) were identified in amniocytes DNA samples from CHD fetuses using high-resolution CMA and copy number variation sequencing (CNV-Seq).
  
  
  RESULTS
  Overall, 21 of 115 CHD fetuses (18.3%) referred for CMA had a pathogenic chromosomal anomaly. In six of 73 fetuses (8.2%) with an isolated CHD, CMA identified two cases of DiGeorge syndrome, and one case each of 1q21.1 microdeletion, 16p11.2 microdeletion and Angelman/Prader Willi syndromes, and 22q11.21 microduplication syndrome. In 12 of 42 fetuses (28.6%) with CHD and additional structural abnormalities, CMA identified eight whole or partial trisomies (19.0%), five CNVs (11.9%) associated with DiGeorge, Wolf-Hirschhorn, Miller-Dieker, Cri du Chat and Blepharophimosis, Ptosis, and Epicanthus Inversus syndromes and four other rare pathogenic CNVs (9.5%). Overall, there was a 100% diagnostic concordance between CMA and CNV-Seq for detecting all 21 pathogenic chromosomal abnormalities associated with CHD.
  
  
  CONCLUSIONS
  CMA and CNV-Seq are reliable and accurate prenatal techniques for identifying pathogenic fetal chromosomal abnormalities associated with cardiac defects. © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Ru
authors.affiliation: Department of Medical Genetics of Nanjing University Medical School, Nanjing, China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Wu
authors.affiliation: Berry Genomics, Beijing, China.
authors.forename: David S
authors.initials: DS
authors.lastname: Cram
authors.affiliation: Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Hu
mesh_terms: D002869:Chromosome Aberrations; D025063:Chromosome Disorders / Q000175:diagnosis*; D056915:DNA Copy Number Variations; D005260:Female; D005820:Genetic Testing / Q000379:methods*; D006330:Heart Defects, Congenital / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D046228:Microarray Analysis / Q000379:methods*; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D011446:Prospective Studies