title: Chromosomal abnormalities and copy number variations in fetal left-sided congenital heart defects.
abstract: OBJECTIVE
  To demonstrate the spectrum of copy number variants (CNVs) in fetuses with isolated left-sided congenital heart defects (CHDs), and analyse genetic content.
  
  
  METHODS
  Between 2003 and 2012, 200 fetuses were identified with left-sided CHD. Exclusion criteria were chromosomal rearrangements, 22q11.2 microdeletion and/or extra-cardiac malformations (n = 64). We included cases with additional minor anomalies (n = 39), such as single umbilical artery. In 54 of 136 eligible cases, stored material was available for array analysis. CNVs were categorized as either (likely) benign, (likely) pathogenic or of unknown significance.
  
  
  RESULTS
  In 18 of the 54 isolated left-sided CHDs we found 28 rare CNVs (prevalence 33%, average 1.6 CNV per person, size 10.6 kb-2.2 Mb). Our interpretation yielded clinically significant CNVs in two of 54 cases (4%) and variants of unknown significance in three other cases (6%).
  
  
  CONCLUSIONS
  In left-sided CHDs that appear isolated, with normal chromosome analysis and 22q11.2 FISH analysis, array analysis detects clinically significant CNVs. When counselling parents of a fetus with a left-sided CHD it must be taken into consideration that aside from the cardiac characteristics, the presence of extra-cardiac malformations and chromosomal abnormalities influence the treatment plan and prognosis.
authors.affiliation: Department of Obstetrics and Fetal Medicine, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Fenna A R
authors.initials: FA
authors.lastname: Jansen
authors.affiliation: Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Mariette J V
authors.initials: MJ
authors.lastname: Hoffer
authors.affiliation: Department of Obstetrics, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Christine L
authors.initials: CL
authors.lastname: van Velzen
authors.affiliation: Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Stephani Klingeman
authors.initials: SK
authors.lastname: Plati
authors.affiliation: Department of Pediatric Cardiology of the Willem Alexander Children's Hospital, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Marry E B
authors.initials: ME
authors.lastname: Rijlaarsdam
authors.affiliation: Department of Pediatric Cardiology of the Emma Children's Hospital, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Sally-Ann B
authors.initials: SA
authors.lastname: Clur
authors.affiliation: Department of Pediatric Cardiology of the Willem Alexander Children's Hospital, Leiden University Medical Center, Leiden, the Netherlands.|Department of Pediatric Cardiology of the Emma Children's Hospital, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Nico A
authors.initials: NA
authors.lastname: Blom
authors.affiliation: Department of Obstetrics, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Eva
authors.initials: E
authors.lastname: Pajkrt
authors.affiliation: Department of Clinical Genetics, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Shama L
authors.initials: SL
authors.lastname: Bhola
authors.affiliation: Department of Clinical Genetics, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Alida C
authors.initials: AC
authors.lastname: Knegt
authors.affiliation: Department of Obstetrics, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Marion A
authors.initials: MA
authors.lastname: de Boer
authors.affiliation: Department of Obstetrics and Fetal Medicine, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Monique C
authors.initials: MC
authors.lastname: Haak
mesh_terms: D001017:Aortic Coarctation / Q000000981:diagnostic imaging / Q000235:genetics; D001024:Aortic Valve Stenosis / Q000151:congenital / Q000000981:diagnostic imaging / Q000235:genetics; D002869:Chromosome Aberrations; D015331:Cohort Studies; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations / Q000235:genetics*; D016208:Databases, Factual; D005260:Female; D006330:Heart Defects, Congenital / Q000000981:diagnostic imaging / Q000235:genetics*; D006801:Humans; D018636:Hypoplastic Left Heart Syndrome / Q000000981:diagnostic imaging / Q000235:genetics; D017404:In Situ Hybridization, Fluorescence; D011247:Pregnancy; D016216:Ultrasonography, Prenatal