Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Sep 11;9(9):454.
doi: 10.3390/genes9090454.

Genetic Imbalances in Argentinean Patients with Congenital Conotruncal Heart Defects

Marisol Delea  1 , Lucía D Espeche  2 , Carlos D Bruque  3   4 , María Paz Bidondo  5 , Lucía S Massara  6 , Jaen Oliveri  7 , Paloma Brun  8 , Viviana R Cosentino  9 , Celeste Martinoli  10 , Norma Tolaba  11 , Claudina Picon  12 , María Eugenia Ponce Zaldua  13 , Silvia Ávila  14 , Viviana Gutnisky  15 , Myriam Perez  16 , Lilian Furforo  17 , Noemí D Buzzalino  18 , Rosa Liascovich  19 , Boris Groisman  20 , Mónica Rittler  21 , Sandra Rozental  22 , Pablo Barbero  23 , Liliana Dain  24   25
Affiliations

Genetic Imbalances in Argentinean Patients with Congenital Conotruncal Heart Defects

Marisol Delea et al. Genes (Basel). .

Abstract

Congenital conotruncal heart defects (CCHD) are a subset of serious congenital heart defects (CHD) of the cardiac outflow tracts or great arteries. Its frequency is estimated in 1/1000 live births, accounting for approximately 10⁻30% of all CHD cases. Chromosomal abnormalities and copy number variants (CNVs) contribute to the disease risk in patients with syndromic and/or non-syndromic forms. Although largely studied in several populations, their frequencies are barely reported for Latin American countries. The aim of this study was to analyze chromosomal abnormalities, 22q11 deletions, and other genomic imbalances in a group of Argentinean patients with CCHD of unknown etiology. A cohort of 219 patients with isolated CCHD or associated with other major anomalies were referred from different provinces of Argentina. Cytogenetic studies, Multiplex-Ligation-Probe-Amplification (MLPA) and fluorescent in situ hybridization (FISH) analysis were performed. No cytogenetic abnormalities were found. 22q11 deletion was found in 23.5% of the patients from our cohort, 66% only had CHD with no other major anomalies. None of the patients with transposition of the great vessels (TGV) carried the 22q11 deletion. Other 4 clinically relevant CNVs were also observed: a distal low copy repeat (LCR)D-E 22q11 duplication, and 17p13.3, 4q35 and TBX1 deletions. In summary, 25.8% of CCHD patients presented imbalances associated with the disease.

Keywords: 22q11 deletion; conotruncal congenital heart defects; copy number variations.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

Figures

Figure 1
Figure 1
Microdeletions and microduplications in the 22q11 region among patients with CCHD. The red rectangle in the ideogram above displays the chromosome 22q11 region included in the analyses. Horizontal red bars indicate deletions, while the blue ones represent duplications. The OMIM genes are in green. Regions involving the different low copy repeats (LCRs) are highlighted in light blue. The imbalances extensions are delimited by vertical black lines. When only one probe from the MLPA kit is deleted or duplicated, only one vertical line is displayed. * This patient also presented a 9q34.3 duplication involving only one probe. ** This patient also presented a deletion involving at least 406 Kb in 4q35.12.
Figure 2
Figure 2
Distribution of 22q11 deletion and other imbalances in the different groups of CCHD studied. Del 22q11 refers to the 3 Mb and 1.5 Mb deletions. CCHD: Conotruncal congenital heart defect; TOF: Tetralogy of Fallot; PTA: Persistent Truncus Arteriosus; TGV: Transposition of the Great Vessels; IAA: Interrupted Aortic Arch; PA + VSD: Pulmonary Atresia with Ventricular Septal Defect; DORV: Double Outlet Right Ventricle; sVSD: Subaortic Ventricular Septal Defect; OII: Other isolated imbalances: refers to imbalances found in patients excluding those observed also with the 22q11 deletion; NI: No imbalances. Inside each chart, the number of patients in each category. Patients who had more than one CHD were included in both categories.
Figure 3
Figure 3
Distribution of the 22q11 deletion in simple or complex CCHD (a) or in CCHD presented as isolated or associated (b). Del 22q11 refers to the 3 Mb and 1.5 Mb deletions. CCHD: Conotruncal congenital heart defects. Inside the charts, numbers of patients in each category. * p < 0.05.
See this image and copyright information in PMC

References

    1. Pierpont M.E., Basson C.T., Benson D.W., Gelb B.D., Giglia T.M., Goldmuntz E., McGee G., Sable C.A., Srivastava D., Webb C.L. Genetic basis for congenital heart defects: current knowledge: a scientific statement from the american heart association congenital cardiac defects committee, council on cardiovascular disease in the young: endorsed by the american academy of pediatrics. Circulation. 2007;115:3015–3038. doi: 10.1161/CIRCULATIONAHA.106.183056. - DOI - PubMed
    1. Bruneau B.G. The developmental genetics of congenital heart disease. Nature. 2008;451:943–948. doi: 10.1038/nature06801. - DOI - PubMed
    1. Groisman B., Bidondo M.P., Duarte S., Piola A., Tardivo A., Liascovich R., Barbero P. Reporte Anual RENAC 2017. Análisis Epidemiológico Sobre las Anomalías Congénitas en Recién Nacidos, Registradas Durante 2016 en la República Argentina. [(accessed on 26 July 2018)]; Available online: http://www.msal.gob.ar/images/stories/bes/graficos/0000001111cnt-2018-02....
    1. Patel S.S., Burns T.L. Nongenetic risk factors and congenital heart defects. Pediatr. Cardiol. 2013;34:1535–1555. doi: 10.1007/s00246-013-0775-4. - DOI - PubMed
    1. Fahed A.C., Gelb B.D., Seidman J.G., Seidman C.E. Genetics of congenital heart disease: the glass half empty. Circ. Res. 2013;112:707–720. doi: 10.1161/CIRCRESAHA.112.300853. - DOI - PMC - PubMed

LinkOut - more resources