Genetic Analysis Algorithm for the Study of Patients with Multiple Congenital Anomalies and Isolated Congenital Heart Disease
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 4.06/1...
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MDPI AG
2022-06-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/13/7/1172 |
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| author | Marisol Delea Lucia S. Massara Lucia D. Espeche María Paz Bidondo Pablo Barbero Jaen Oliveri Paloma Brun Mónica Fabro Micaela Galain Cecilia S. Fernández Melisa Taboas Carlos D. Bruque Jorge E. Kolomenski Agustín Izquierdo Ariel Berenstein Viviana Cosentino Celeste Martinoli Mariana Vilas Mónica Rittler Rodrigo Mendez Lilian Furforo Rosa Liascovich Boris Groisman Sandra Rozental Liliana Dain on behalf of the PID ACM-CC Group |
| author_facet | Marisol Delea Lucia S. Massara Lucia D. Espeche María Paz Bidondo Pablo Barbero Jaen Oliveri Paloma Brun Mónica Fabro Micaela Galain Cecilia S. Fernández Melisa Taboas Carlos D. Bruque Jorge E. Kolomenski Agustín Izquierdo Ariel Berenstein Viviana Cosentino Celeste Martinoli Mariana Vilas Mónica Rittler Rodrigo Mendez Lilian Furforo Rosa Liascovich Boris Groisman Sandra Rozental Liliana Dain on behalf of the PID ACM-CC Group |
| author_sort | Marisol Delea |
| collection | DOAJ |
| description | 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 <i>TBX1</i> gene deletion. Following NGS analysis, 12 patients presented pathogenic or likely pathogenic genetic variants, five of them, found in <i>KAT6B</i>, <i>SHH</i>, <i>MYH11</i>, <i>MYH7</i> and <i>EP300</i> 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. |
| first_indexed | 2024-03-09T03:24:02Z |
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| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-09T03:24:02Z |
| publishDate | 2022-06-01 |
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| spelling | doaj.art-f2678ee718c74b60a45275740230ff8d2023-12-03T15:05:47ZengMDPI AGGenes2073-44252022-06-01137117210.3390/genes13071172Genetic Analysis Algorithm for the Study of Patients with Multiple Congenital Anomalies and Isolated Congenital Heart DiseaseMarisol Delea0Lucia S. Massara1Lucia D. Espeche2María Paz Bidondo3Pablo Barbero4Jaen Oliveri5Paloma Brun6Mónica Fabro7Micaela Galain8Cecilia S. Fernández9Melisa Taboas10Carlos D. Bruque11Jorge E. Kolomenski12Agustín Izquierdo13Ariel Berenstein14Viviana Cosentino15Celeste Martinoli16Mariana Vilas17Mónica Rittler18Rodrigo Mendez19Lilian Furforo20Rosa Liascovich21Boris Groisman22Sandra Rozental23Liliana Dain24on behalf of the PID ACM-CC GroupCentro Nacional de Genética Médica “Dr. Eduardo Castilla”- ANLIS “Dr. Carlos G. Malbrán”, Avda. Las Heras 2670, Buenos Aires 1425, ArgentinaHospital de Alta Complejidad en Red El Cruce—SAMIC. Av. Calchaquí 5401, Florencio Varela 1888, ArgentinaCentro Nacional de Genética Médica “Dr. Eduardo Castilla”- ANLIS “Dr. Carlos G. Malbrán”, Avda. Las Heras 2670, Buenos Aires 1425, ArgentinaCentro Nacional de Genética Médica “Dr. Eduardo Castilla”- ANLIS “Dr. Carlos G. Malbrán”, Avda. Las Heras 2670, Buenos Aires 1425, ArgentinaCentro Nacional de Genética Médica “Dr. Eduardo Castilla”- ANLIS “Dr. Carlos G. Malbrán”, Avda. Las Heras 2670, Buenos Aires 1425, ArgentinaHospital de Alta Complejidad en Red El Cruce—SAMIC. Av. Calchaquí 5401, Florencio Varela 1888, ArgentinaHospital de Alta Complejidad en Red El Cruce—SAMIC. Av. Calchaquí 5401, Florencio Varela 1888, ArgentinaNovagen, Viamonte 1430, Buenos Aires 1055, ArgentinaNovagen, Viamonte 1430, Buenos Aires 1055, ArgentinaNovagen, Viamonte 1430, Buenos Aires 1055, ArgentinaCentro Nacional de Genética Médica “Dr. Eduardo Castilla”- ANLIS “Dr. Carlos G. Malbrán”, Avda. Las Heras 2670, Buenos Aires 1425, ArgentinaCentro Nacional de Genética Médica “Dr. Eduardo Castilla”- ANLIS “Dr. Carlos G. Malbrán”, Avda. Las Heras 2670, Buenos Aires 1425, ArgentinaDepartamento de Fisiología, Biología Molecular y Celular, Instituto de Biociencias, Biotecnología y Biología Traslacional (iB3), Facultad de Ciencias Exactas y Naturales-UBA, Intendente Güiraldes 2160, Buenos Aires 1428, ArgentinaCentro de Investigaciones Endocrinológicas “Dr. César Bergadá”. Gallo 1330, Buenos Aires 1425, ArgentinaInstituto Multidisciplinario de Investigaciones en Patologías Pediátricas, Gallo 1330, Buenos Aires 1425, ArgentinaHospital Interzonal General de Agudos Luisa Cravenna de Gandulfo, Balcarce 351, Lomas de Zamora 1832, ArgentinaHospital Sor Maria Ludovica, Calle 14 1631, La Plata 1904, ArgentinaHospital Materno Infantil Ramón Sardá, Esteban de Luca 2151, Buenos Aires 1246, ArgentinaHospital Materno Infantil Ramón Sardá, Esteban de Luca 2151, Buenos Aires 1246, ArgentinaCentro Nacional de Genética Médica “Dr. Eduardo Castilla”- ANLIS “Dr. Carlos G. Malbrán”, Avda. Las Heras 2670, Buenos Aires 1425, ArgentinaHospital Materno Infantil Ramón Sardá, Esteban de Luca 2151, Buenos Aires 1246, ArgentinaCentro Nacional de Genética Médica “Dr. Eduardo Castilla”- ANLIS “Dr. Carlos G. Malbrán”, Avda. Las Heras 2670, Buenos Aires 1425, ArgentinaCentro Nacional de Genética Médica “Dr. Eduardo Castilla”- ANLIS “Dr. Carlos G. Malbrán”, Avda. Las Heras 2670, Buenos Aires 1425, ArgentinaCentro Nacional de Genética Médica “Dr. Eduardo Castilla”- ANLIS “Dr. Carlos G. Malbrán”, Avda. Las Heras 2670, Buenos Aires 1425, ArgentinaCentro Nacional de Genética Médica “Dr. Eduardo Castilla”- ANLIS “Dr. Carlos G. Malbrán”, Avda. Las Heras 2670, Buenos Aires 1425, ArgentinaCongenital 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 <i>TBX1</i> gene deletion. Following NGS analysis, 12 patients presented pathogenic or likely pathogenic genetic variants, five of them, found in <i>KAT6B</i>, <i>SHH</i>, <i>MYH11</i>, <i>MYH7</i> and <i>EP300</i> 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.https://www.mdpi.com/2073-4425/13/7/1172multiple congenital anomaliescongenital heart diseasechromosomal abnormalitiesarray-CGHnext-generation sequencing |
| spellingShingle | Marisol Delea Lucia S. Massara Lucia D. Espeche María Paz Bidondo Pablo Barbero Jaen Oliveri Paloma Brun Mónica Fabro Micaela Galain Cecilia S. Fernández Melisa Taboas Carlos D. Bruque Jorge E. Kolomenski Agustín Izquierdo Ariel Berenstein Viviana Cosentino Celeste Martinoli Mariana Vilas Mónica Rittler Rodrigo Mendez Lilian Furforo Rosa Liascovich Boris Groisman Sandra Rozental Liliana Dain on behalf of the PID ACM-CC Group Genetic Analysis Algorithm for the Study of Patients with Multiple Congenital Anomalies and Isolated Congenital Heart Disease Genes multiple congenital anomalies congenital heart disease chromosomal abnormalities array-CGH next-generation sequencing |
| title | Genetic Analysis Algorithm for the Study of Patients with Multiple Congenital Anomalies and Isolated Congenital Heart Disease |
| title_full | Genetic Analysis Algorithm for the Study of Patients with Multiple Congenital Anomalies and Isolated Congenital Heart Disease |
| title_fullStr | Genetic Analysis Algorithm for the Study of Patients with Multiple Congenital Anomalies and Isolated Congenital Heart Disease |
| title_full_unstemmed | Genetic Analysis Algorithm for the Study of Patients with Multiple Congenital Anomalies and Isolated Congenital Heart Disease |
| title_short | Genetic Analysis Algorithm for the Study of Patients with Multiple Congenital Anomalies and Isolated Congenital Heart Disease |
| title_sort | genetic analysis algorithm for the study of patients with multiple congenital anomalies and isolated congenital heart disease |
| topic | multiple congenital anomalies congenital heart disease chromosomal abnormalities array-CGH next-generation sequencing |
| url | https://www.mdpi.com/2073-4425/13/7/1172 |
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