title: Submicroscopic chromosomal imbalances detected by array-CGH are a frequent cause of congenital heart defects in selected patients.
abstract: OBJECTIVE
  Congenital heart defects (CHDs) are frequently caused by chromosomal imbalances, especially when associated with additional malformations, dysmorphism, or developmental delay. Only in a subset of such patients, a chromosomal aberration can be identified with current cytogenetic tests. Array Comparative Genomic Hybridization (Array-CGH) now enables the detection of submicroscopic chromosomal imbalances at high resolution. In this report, we evaluate for the first time the use of array-CGH as a diagnostic tool in a selected group of patients with a CHD.
  
  
  RESULTS
  Sixty patients with a CHD of unknown cause but with features suggestive of a chromosomal aberration were selected. Array-CGH was performed using an in-house made 1 Mb micro-array. Chromosomal imbalances not previously described as polymorphisms were detected in 18/60 patients (30%). Ten of these (17%) are considered to be causal. In three deletions, genes known to cause CHDs were implicated (NKX2.5, NOTCH1, NSD1, EHMT). One patient carried a duplication of chromosome 22q11.2, previously associated with CHD. In the other six patients, both the de novo occurrence as well as the size of the imbalance indicated causality. In addition, seven inherited aberrations unreported thus far were detected. Their causal relationship with CHDs remains to be established. Finally, a mosaic monosomy 7 was not considered as causal but did enable to make a diagnosis of Fanconi anaemia.
  
  
  CONCLUSIONS
  This study shows that array-CGH is able to provide an etiological diagnosis in a large proportion of patients with a CHD, selected for a 'chromosomal phenotype'. Besides their usefulness in genetic counselling, identified chromosomal aberrations may aid in the medical follow-up of these individuals.
authors: Center for Human Genetics, Catholic University of Leuven, Belgium.
authors: Bernard
authors: B
authors: Thienpont
authors: Luc
authors: L
authors: Mertens
authors: Thomy
authors: T
authors: de Ravel
authors: Benedicte
authors: B
authors: Eyskens
authors: Derize
authors: D
authors: Boshoff
authors: Nicole
authors: N
authors: Maas
authors: Jean-Pierre
authors: JP
authors: Fryns
authors: Marc
authors: M
authors: Gewillig
authors: Joris R
authors: JR
authors: Vermeesch
authors: Koen
authors: K
authors: Devriendt
mesh_terms: D002869:Chromosome Aberrations; D020732:Cytogenetic Analysis / Q000379:methods; D006330:Heart Defects, Congenital / Q000235:genetics*; D006801:Humans; D010641:Phenotype; D016133:Polymerase Chain Reaction / Q000379:methods