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

TY - JOUR

T1 - High frequency of submicroscopic genomic aberrations detected by tiling path array comparative genome hybridisation in patients with isolated congenital heart disease

AU - Erdogan, F

AU - Larsen, Lars Allan

AU - Zhang, L

AU - Tümer, Z

AU - Tommerup, N

AU - Chen, W

AU - Jacobsen, J R

AU - Schubert, M

AU - Jurkatis, J

AU - Tzschach, A

AU - Ropers, H-H

AU - Ullmann, R

N1 - Keywords: Child; Chromosome Aberrations; Chromosome Deletion; Comparative Genomic Hybridization; Cytogenetic Analysis; Female; Gene Dosage; Gene Duplication; Genome, Human; Heart Defects, Congenital; Humans; Infant; Infant, Newborn; Male; Oligonucleotide Array Sequence Analysis; Phenotype

PY - 2008

Y1 - 2008

N2 - 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.

AB - 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.

U2 - 10.1136/jmg.2008.058776

DO - 10.1136/jmg.2008.058776

M3 - Journal article

C2 - 18713793

SN - 0022-2593

VL - 45

SP - 704

EP - 709

JO - Journal of Medical Genetics

JF - Journal of Medical Genetics

IS - 11

ER -