Genomic imbalances in syndromic congenital heart disease.

To identify pathogenic genomic imbalances in patients presenting congenital heart disease (CHD) with extra cardiac anomalies and exclusion of 22q11.2 deletion syndrome (22q11.2 DS). 78 patients negative for the 22q11.2 deletion, previously screened by fluorescence in situ hybridization (FISH) and/or multiplex ligation probe amplification (MLPA) were tested by chromosomal microarray analysis (CMA). Clinically significant copy number variations (CNVs ≥300kb) were identified in 10% (8/78) of cases. In addition, potentially relevant CNVs were detected in two cases (993kb duplication in 15q21.1 and 706kb duplication in 2p22.3). Genes inside the CNV regions found in this study, such as IRX4, BMPR1A, SORBS2, ID2, ROCK2, E2F6, GATA4, SOX7, SEMAD6D, FBN1, and LTPB1 are known to participate in cardiac development and could be candidate genes for CHD. These data showed that patients presenting CHD with extra cardiac anomalies and exclusion of 22q11.2 DS should be investigated by CMA. The present study emphasizes the possible role of CNVs in CHD.

Molck MC ，Simioni M ，Paiva Vieira T ，Sgardioli IC ，Paoli Monteiro F ，Souza J ，Fett-Conte AC ，Félix TM ，Lopes Monlléo I ，Gil-da-Silva-Lopes VL ... -  《-》

A modified multiplex ligation-dependent probe amplification method for the detection of 22q11.2 copy number variations in patients with congenital heart disease.

Zhang X ，Xu Y ，Liu D ，Geng J ，Chen S ，Jiang Z ，Fu Q ，Sun K ... -  《BMC GENOMICS》

Screening of copy number variants in the 22q11.2 region of congenital heart disease patients from the São Miguel Island, Azores, revealed the second patient with a triplication.

Pires R ，Pires LM ，Vaz SO ，Maciel P ，Anjos R ，Moniz R ，Branco CC ，Cabral R ，Carreira IM ，Mota-Vieira L ... -  《BMC GENETICS》

Analysis of gene copy number variations in patients with congenital heart disease using multiplex ligation-dependent probe amplification.

Mutlu ET ，Aykan HH ，Karagöz T 《-》

Copy number variants detection by microarray and multiplex ligation-dependent probe amplification in congenital heart diseases.

Congenital heart diseases (CHDs) are the most common birth defects among life births, which could be presented as isolated or syndromic with other congenital malformations. The etiology of CHD largely unknown, genetic and environmental factors contribute to the disease. Recurrent copy number variants (CNVs) have been reported in the pathogenesis of CHD. The aim of this study was to evaluate the clinical utility of multiplex ligation-dependent probe amplification (MLPA) and microarray analyses on isolated and syndromic CHD cases and to explore the relationship between identified CNVs and CHD. Eighteen prenatal samples, 16 isolated and 33 syndromic patients with mild to severe CHD phenotype were tested. Prenatal and isolated CHD cases did not show pathogenic CNVs. Clinically significant CNVs were detected in 7/33 (21%) syndromic CHD patients: del 22q11.2 (n = 2), 8p23.1 duplication (n = 2), deletion 5p (n = 1), deletion 6q21q22 (n = 1), unbalanced translocation causing partial deletion of 4q34.3 and duplication of 6q25.1 (n = 1). These genomic imbalances contain genes that has been associated with human CHD before. The present study demonstrates that using microarray and MLPA analysis increase the detection rate of causal CNVs in individuals with syndromic CHD.

Nagy O ，Szakszon K ，Biró BO ，Mogyorósy G ，Nagy D ，Nagy B ，Balogh I ，Ujfalusi A ... -  《-》