Genetic Imbalances in Argentinean Patients with Congenital Conotruncal Heart Defects

Marisol Delea,Lilian Furforo,Jaen Oliveri,Noemí Buzzalino,Sandra Rozental,Claudina Picon,Paloma Brun,Viviana Cosentino,Rosa Liascovich,Boris Groisman,Celeste Martinoli,Norma Tolaba,Pablo Barbero,María Paz Bidondo ,Lucía D Espeche ,María Eugenia Ponce Zaldua ,Viviana J Gutnisky ,Lucía S Massara ,Carlos David Bruque ,Sílvia Ávila ,Mónica Rittler,M Vaquero Pérez ,Liliana Daín

doi:10.3390/genes9090454

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.

Highlights

Congenital heart defects (CHD) are a group of structural anomalies of the heart and blood vessels that arise during cardiac embryogenesis and differ in morphology, physiology, and clinical outcome.Congenital heart defects are the most common type of birth defect and one of the major causes of perinatal mortality, with a worldwide prevalence of 1 per 125 births [1,2]
Two hundred and nineteen patients who fulfilled the inclusion criteria were referred to ascertain the genetic causes of conotruncal heart defects (CCHD)
When analyzing the presence of other cardiac anomalies in our patients, we found no differences in the frequencies of 22q11 deletion patients, it was significantly higher in those who presented at least another extracardiac major anomaly

Summary

Introduction

Congenital heart defects are the most common type of birth defect and one of the major causes of perinatal mortality, with a worldwide prevalence of 1 per 125 births [1,2]. CHD from a total of 305,452 births, which represents a prevalence of 11.52 affected newborns per. Congenital heart defects include a broad spectrum of malformations that can occur isolated or associated with other malformations. Though CHD pathogenesis is largely unknown, it is widely reported that genetic and non-genetic factors may play an important role [4,5]. Among non-genetic causes, environmental teratogens, maternal exposure to alcohol, thalidomide, seizure medications, infectious agents as rubella, obesity, diabetes mellitus and/or maternal phenylketonuria are recognized as emerging risk factors for CHD [4]

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