A Robust and Comprehensive Study of the Molecular and Genetic Basis of Neurodevelopmental Delay in a Sample of 3244 Patients, Evaluated by Exome Analysis in a Latin Population
<b>Background and Objectives</b>: Neurodevelopmental disorders (NDDs), including developmental delay (DD), autism spectrum disorder (ASD), intellectual disability (ID), attention-deficit/hyperactivity disorder (ADHD), and specific learning disorders, affect 15% of children and adolescent...
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2025-02-01
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| author | Julian Lamilla Taryn A. Castro-Cuesta Paula Rueda-Gaitán Laura Camila Rios Pinto Diego Alejandro Rodríguez Gutiérrez Yuri Natalia Sanchez Rubio Carlos Estrada-Serrato Olga Londoño Cynthia Rucinski Mauricio Arcos-Burgos Mario Isaza-Ruget Juan Javier López Rivera |
| author_facet | Julian Lamilla Taryn A. Castro-Cuesta Paula Rueda-Gaitán Laura Camila Rios Pinto Diego Alejandro Rodríguez Gutiérrez Yuri Natalia Sanchez Rubio Carlos Estrada-Serrato Olga Londoño Cynthia Rucinski Mauricio Arcos-Burgos Mario Isaza-Ruget Juan Javier López Rivera |
| author_sort | Julian Lamilla |
| collection | DOAJ |
| description | <b>Background and Objectives</b>: Neurodevelopmental disorders (NDDs), including developmental delay (DD), autism spectrum disorder (ASD), intellectual disability (ID), attention-deficit/hyperactivity disorder (ADHD), and specific learning disorders, affect 15% of children and adolescents worldwide. Advances in next-generation sequencing, particularly whole exome sequencing (WES), have improved the understanding of NDD genetics. <b>Methodology</b>: This study analyzed 3244 patients undergoing WES (single, duo, trio analyses), with 1028 meeting inclusion criteria (67% male; aged 0–50 years). <b>Results</b>: Pathogenic (P) or likely pathogenic (LP) variants were identified in 190 patients, achieving a diagnostic yield of 13.4% (singleton), 14% (duo), and 21.2% (trio). A total of 207 P/LP variants were identified in NDD-associated genes: 38% were missense (48 de novo), 29% frameshift (26 de novo), 21% nonsense (14 de novo), 11% splicing site (14 de novo), and 1% inframe (1 de novo). De novo variants accounted for 49.8% of cases, with 86 novels de novo variants and 27 novel non de novo variants unreported in databases like ClinVar or scientific literature. <b>Conclusions</b>: This is the largest study on WES in Colombian children with NDDs and one of the largest in Latino populations. It highlights WES as a cost-effective first-tier diagnostic tool in low-income settings, reducing diagnostic timelines and improving clinical care. These findings underscore the feasibility of implementing WES in underserved populations and contribute significantly to understanding NDD genetics, identifying novel variants with potential for further research and clinical applications. |
| format | Article |
| id | doaj-art-a43ab4d8a8564be7b153817c6fa92b6f |
| institution | OA Journals |
| issn | 2075-4418 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | MDPI AG |
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| series | Diagnostics |
| spelling | doaj-art-a43ab4d8a8564be7b153817c6fa92b6f2025-08-20T02:12:41ZengMDPI AGDiagnostics2075-44182025-02-0115337610.3390/diagnostics15030376A Robust and Comprehensive Study of the Molecular and Genetic Basis of Neurodevelopmental Delay in a Sample of 3244 Patients, Evaluated by Exome Analysis in a Latin PopulationJulian Lamilla0Taryn A. Castro-Cuesta1Paula Rueda-Gaitán2Laura Camila Rios Pinto3Diego Alejandro Rodríguez Gutiérrez4Yuri Natalia Sanchez Rubio5Carlos Estrada-Serrato6Olga Londoño7Cynthia Rucinski8Mauricio Arcos-Burgos9Mario Isaza-Ruget10Juan Javier López Rivera11Laboratorio Clínico Especializado, Clínica Universitaria Colombia, Clínica Colsanitas, Bogotá 111321, ColombiaLaboratorio Clínico Especializado, Clínica Universitaria Colombia, Clínica Colsanitas, Bogotá 111321, ColombiaLaboratorio Clínico Especializado, Clínica Universitaria Colombia, Clínica Colsanitas, Bogotá 111321, ColombiaLaboratorio Clínico Especializado, Clínica Universitaria Colombia, Clínica Colsanitas, Bogotá 111321, ColombiaLaboratorio Clínico Especializado, Clínica Universitaria Colombia, Clínica Colsanitas, Bogotá 111321, ColombiaLaboratorio Clínico Especializado, Clínica Universitaria Colombia, Clínica Colsanitas, Bogotá 111321, ColombiaLaboratorio Clínico Especializado, Clínica Universitaria Colombia, Clínica Colsanitas, Bogotá 111321, ColombiaLaboratorio Clínico Especializado, Clínica Universitaria Colombia, Clínica Colsanitas, Bogotá 111321, ColombiaLaboratorio Clínico Especializado, Clínica Universitaria Colombia, Clínica Colsanitas, Bogotá 111321, ColombiaLaboratorio Clínico Especializado, Clínica Universitaria Colombia, Clínica Colsanitas, Bogotá 111321, ColombiaGrupo de Genética Médica, Clínica Universitaria Colombia, Clínica Colsanitas, Bogotá 111321, ColombiaLaboratorio Clínico Especializado, Clínica Universitaria Colombia, Clínica Colsanitas, Bogotá 111321, Colombia<b>Background and Objectives</b>: Neurodevelopmental disorders (NDDs), including developmental delay (DD), autism spectrum disorder (ASD), intellectual disability (ID), attention-deficit/hyperactivity disorder (ADHD), and specific learning disorders, affect 15% of children and adolescents worldwide. Advances in next-generation sequencing, particularly whole exome sequencing (WES), have improved the understanding of NDD genetics. <b>Methodology</b>: This study analyzed 3244 patients undergoing WES (single, duo, trio analyses), with 1028 meeting inclusion criteria (67% male; aged 0–50 years). <b>Results</b>: Pathogenic (P) or likely pathogenic (LP) variants were identified in 190 patients, achieving a diagnostic yield of 13.4% (singleton), 14% (duo), and 21.2% (trio). A total of 207 P/LP variants were identified in NDD-associated genes: 38% were missense (48 de novo), 29% frameshift (26 de novo), 21% nonsense (14 de novo), 11% splicing site (14 de novo), and 1% inframe (1 de novo). De novo variants accounted for 49.8% of cases, with 86 novels de novo variants and 27 novel non de novo variants unreported in databases like ClinVar or scientific literature. <b>Conclusions</b>: This is the largest study on WES in Colombian children with NDDs and one of the largest in Latino populations. It highlights WES as a cost-effective first-tier diagnostic tool in low-income settings, reducing diagnostic timelines and improving clinical care. These findings underscore the feasibility of implementing WES in underserved populations and contribute significantly to understanding NDD genetics, identifying novel variants with potential for further research and clinical applications.https://www.mdpi.com/2075-4418/15/3/376neurodevelopmental disorderswhole exome sequencinggenetic testing |
| spellingShingle | Julian Lamilla Taryn A. Castro-Cuesta Paula Rueda-Gaitán Laura Camila Rios Pinto Diego Alejandro Rodríguez Gutiérrez Yuri Natalia Sanchez Rubio Carlos Estrada-Serrato Olga Londoño Cynthia Rucinski Mauricio Arcos-Burgos Mario Isaza-Ruget Juan Javier López Rivera A Robust and Comprehensive Study of the Molecular and Genetic Basis of Neurodevelopmental Delay in a Sample of 3244 Patients, Evaluated by Exome Analysis in a Latin Population Diagnostics neurodevelopmental disorders whole exome sequencing genetic testing |
| title | A Robust and Comprehensive Study of the Molecular and Genetic Basis of Neurodevelopmental Delay in a Sample of 3244 Patients, Evaluated by Exome Analysis in a Latin Population |
| title_full | A Robust and Comprehensive Study of the Molecular and Genetic Basis of Neurodevelopmental Delay in a Sample of 3244 Patients, Evaluated by Exome Analysis in a Latin Population |
| title_fullStr | A Robust and Comprehensive Study of the Molecular and Genetic Basis of Neurodevelopmental Delay in a Sample of 3244 Patients, Evaluated by Exome Analysis in a Latin Population |
| title_full_unstemmed | A Robust and Comprehensive Study of the Molecular and Genetic Basis of Neurodevelopmental Delay in a Sample of 3244 Patients, Evaluated by Exome Analysis in a Latin Population |
| title_short | A Robust and Comprehensive Study of the Molecular and Genetic Basis of Neurodevelopmental Delay in a Sample of 3244 Patients, Evaluated by Exome Analysis in a Latin Population |
| title_sort | robust and comprehensive study of the molecular and genetic basis of neurodevelopmental delay in a sample of 3244 patients evaluated by exome analysis in a latin population |
| topic | neurodevelopmental disorders whole exome sequencing genetic testing |
| url | https://www.mdpi.com/2075-4418/15/3/376 |
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