Title: Challenges of Interpreting Copy Number Variation in Syndromic and Non-Syndromic Congenital Heart Defects
Authors: Breckpot, Jeroen ×
Thienpont, Bernard
Arens, Y
Tranchevent, Léon-Charles
Vermeesch, Joris
Moreau, Yves
Gewillig, Marc
Devriendt, Koenraad #
Issue Date: Sep-2011
Publisher: S. Karger
Series Title: Cytogenetic and Genome Research vol:135 issue:3-4 pages:251-259
Abstract: Array comparative genomic hybridization (aCGH) has led to an increased detection of causal chromosomal imbalances in individuals with congenital heart defects (CHD). The introduction of aCGH as a diagnostic tool in a clinical cardiogenetic setting entails numerous challenges. Based on our own experience as well as those of others described in the literature, we outline the state of the art and attempt to answer a number of outstanding questions such as the detection frequency of causal imbalances in different patient populations, the added value of higher-resolution arrays, and the existence of predictive factors in syndromic cases. We introduce a step-by-step approach for clinical interpretation of copy number variants (CNV) detected in CHD, which is primarily based on gene content and overlap with known chromosomal syndromes, rather than on CNV inheritance and size. Based on this algorithm, we have reclassified the detected aberrations in aCGH studies for their causality for syndromic and non-syndromic CHD. From this literature overview, supplemented with own investigations in a cohort of 46 sporadic patients with severe non-syndromic CHD, it seems clear that the frequency of causal CNVs in non-syndromic CHD populations is lower than that in syndromic CNV populations (3.6 vs. 19%). Moreover, causal CNVs in non-syndromic CHD mostly involve imbalances with a moderate effect size and reduced penetrance, whereas the majority of causal imbalances in syndromic CHD consistently affects human development and significantly reduces reproductive fitness.
ISSN: 1424-8581
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Translational Genetics (VIB-KU Leuven Center for Cancer Biology)
Department of Human Genetics - miscellaneous
Laboratory for Genetics of Human Development
ESAT - STADIUS, Stadius Centre for Dynamical Systems, Signal Processing and Data Analytics
Cardiovascular Developmental Biology
× corresponding author
# (joint) last author

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