High frequency of submicroscopic genomic aberrations detected by tiling path array comparative genome hybridisation in patients with isolated congenital heart disease

Item Type:	Article
Title:	High frequency of submicroscopic genomic aberrations detected by tiling path array comparative genome hybridisation in patients with isolated congenital heart disease
Creators Name:	Erdogan, F. and Larsen, L.A. and Zhang, L. and Tuemer, Z. and Tommerup, N. and Chen, W. and Jacobsen, J.R. and Schubert, M. and Jurkatis, J. and Tzschach, A. and Ropers, H.H. and Ullmann, R.
Abstract:	BACKGROUND: Congenital heart disease (CHD) is the most common birth defect and affects nearly 1% of newborns. The aetiology of CHD is largely unknown and only a small percentage can be assigned to environmental risk factors such as maternal diseases or exposure to mutagenic agents during pregnancy. Chromosomal imbalances have been identified in many forms of syndromic CHD, but very little is known about the impact of DNA copy number changes in non-syndromic CHD. METHOD: A sub-megabase resolution array comparative genome hybridisation (CGH) screen was carried out on 105 patients with CHD as the sole abnormality at the time of diagnosis. RESULTS: There were 18 chromosomal changes detected, which do not coincide with common DNA copy number variants, including one de novo deletion, two de novo duplications and eight familial copy number variations (one deletion and seven duplications). CONCLUSIONS: Our data show that submicroscopic deletions and duplications play an important role in the aetiology of this condition, either as direct causes or as genetic risk factors for CHD. These findings have immediate consequences for genetic counselling and should pave the way for the elucidation of the pathogenetic mechanisms underlying CHD.
Keywords:	Chromosome Aberrations, Chromosome Deletion, Comparative Genomic Hybridization, Cytogenetic Analysis, Gene Dosage, Gene Duplication, Human Genome, Congenital Heart Defects, Oligonucleotide Array Sequence Analysis, Phenotype
Source:	Journal of Medical Genetics
ISSN:	0022-2593
Publisher:	BMJ Publishing Group
Volume:	45
Number:	11
Page Range:	704-709
Date:	November 2008
Official Publication:	https://doi.org/10.1136/jmg.2008.058776
PubMed:	View item in PubMed

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