Genetic Analysis Algorithm for the Study of Patients with Multiple Congenital Anomalies and Isolated Congenital Heart Disease

• Published in: Genes Vol. 13; no. 7; p. 1172
• Main Authors: Delea, Marisol, Massara, Lucia S, Espeche, Lucia D, Bidondo, María Paz, Barbero, Pablo, Oliveri, Jaen, Brun, Paloma, Fabro, Mónica, Galain, Micaela, Fernández, Cecilia S, Taboas, Melisa, Bruque, Carlos D, Kolomenski, Jorge E, Izquierdo, Agustín, Berenstein, Ariel, Cosentino, Viviana, Martinoli, Celeste, Vilas, Mariana, Rittler, Mónica, Mendez, Rodrigo, Furforo, Lilian, Liascovich, Rosa, Groisman, Boris, Rozental, Sandra, Dain, Liliana, On Behalf Of The Pid Acm-Cc Group
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 29-06-2022; MDPI
• Subjects: Abnormalities, Multiple - genetics; Algorithms; Birth defects; Births; Care and treatment; Congenital defects; Congenital diseases; Coronary artery disease; Cytogenetics; Diagnosis; Etiology; Gene deletion; Genes; Genetic analysis; Genetic aspects; Genetic diversity; Genetic Testing; Genomes; Genomics; Genotype & phenotype; Health aspects; Heart Defects, Congenital - genetics; Heart diseases; Histone Acetyltransferases; Humans; Infant mortality; Infants; Karyotyping; Methods; Morphology; Mortality; Neonates; Newborn babies; Next-generation sequencing; Patient outcomes; Patients; Peripheral blood; Phenotypes; Tbx1 protein; Argentina; United States > US; congenital heart disease; multiple congenital anomalies; chromosomal abnormalities; next-generation sequencing; array-CGH
• ISSN: 2073-4425; 2073-4425
• DOI: 10.3390/genes13071172

Congenital anomalies (CA) affect 3-5% of newborns, representing the second-leading cause of infant mortality in Argentina. Multiple congenital anomalies (MCA) have a prevalence of 2.26/1000 births in newborns, while congenital heart diseases (CHD) are the most frequent CA with a prevalence of 4.06/1000 births. The aim of this study was to identify the genetic causes in Argentinian patients with MCA and isolated CHD. We recruited 366 patients (172 with MCA and 194 with isolated CHD) born between June 2015 and August 2019 at public hospitals. DNA from peripheral blood was obtained from all patients, while karyotyping was performed in patients with MCA. Samples from patients presenting conotruncal CHD or DiGeorge phenotype (n = 137) were studied using MLPA. Ninety-three samples were studied by array-CGH and 18 by targeted or exome next-generation sequencing (NGS). A total of 240 patients were successfully studied using at least one technique. Cytogenetic abnormalities were observed in 13 patients, while 18 had clinically relevant imbalances detected by array-CGH. After MLPA, 26 patients presented 22q11 deletions or duplications and one presented a
gene deletion. Following NGS analysis, 12 patients presented pathogenic or likely pathogenic genetic variants, five of them, found in
,
,
,
and
genes, are novel. Using an algorithm that combines molecular techniques with clinical and genetic assessment, we determined the genetic contribution in 27.5% of the analyzed patients.