title: Assessment of the role of copy-number variants in 150 patients with congenital heart defects.
abstract: BACKGROUND
  Congenital heart defects are the most common group of major birth anomalies and one of the leading causes of infant deaths. Mendelian and chromosomal syndromes account for about 20% of congenital heart defects and in some cases are associated with other malformations, intellectual disability, and/or dysmorphic features. The remarkable conservation of genetic pathways regulating heart development in animals suggests that genetic factors can be responsible for a significantly higher percentage of cases.
  
  
  OBJECTIVE
  Assessment of the role of CNVs in the etiology of congenital heart defects using microarray studies.
  
  
  METHODS
  Genome-wide array comparative genomic hybridization, targeting genes known to play an important role in heart development or responsible for abnormal cardiac phenotype was used in the study on 150 patients. In addition, we have used multiplex ligation-dependent probe amplification specific for chromosome 22q11.2 region.
  
  
  RESULTS
  We have identified 21 copy-number variants, including 13 known causative recurrent rearrangements (12 deletions 22q11.2 and one deletion 7q11.23), three potentially pathogenic duplications (5q14.2, 15q13.3, and 22q11.2), and five variants likely benign for cardiac anomalies. We suggest that abnormal copy-number of the ARRDC3 and KLF13 genes can be responsible for heart defects.
  
  
  CONCLUSIONS
  Our study demonstrates that array comparative genomic hybridization enables detection of clinically significant chromosomal imbalances in patients with congenital heart defects.
authors: Department of Medical Genetics, Institute of Mother and Child, ul. Kasprzaka 17a, 01-211, Warsaw.
authors: Katarzyna
authors: K
authors: Derwińska
authors: Magdalena
authors: M
authors: Bartnik
authors: Barbara
authors: B
authors: Wiśniowiecka-Kowalnik
authors: Mateusz
authors: M
authors: Jagła
authors: Andrzej
authors: A
authors: Rudziński
authors: Jacek J
authors: JJ
authors: Pietrzyk
authors: Wanda
authors: W
authors: Kawalec
authors: Lidia
authors: L
authors: Ziółkowska
authors: Anna
authors: A
authors: Kutkowska-Kaźmierczak
authors: Tomasz
authors: T
authors: Gambin
authors: Maciej
authors: M
authors: Sykulski
authors: Chad A
authors: CA
authors: Shaw
authors: Anna
authors: A
authors: Gambin
authors: Tadeusz
authors: T
authors: Mazurczak
authors: Ewa
authors: E
authors: Obersztyn
authors: Ewa
authors: E
authors: Bocian
authors: Paweł
authors: P
authors: Stankiewicz
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D056915:DNA Copy Number Variations; D005260:Female; D006330:Heart Defects, Congenital / Q000235:genetics*; D006801:Humans; D008297:Male; D060885:Multiplex Polymerase Chain Reaction; D055815:Young Adult