Phenotypic Complexity and Diagnostic Utility of Exome Sequencing in ASD: Real-World Insights from Colombia
- 1Laboratorio Clínico y de Patología, Clínica Colsanitas, Bogotá 111321, Colombia
- 2Fundación Universitaria Sanitas, Bogotá 110141, Colombia
Abstract
Autism spectrum disorder (ASD) is a genetically heterogeneous condition; however, genomic data from Latin American populations remain limited. We investigated the molecular and phenotypic landscape of ASD in 916 Colombian patients who underwent whole-exome sequencing (WES) between 2022 and 2025. Clinical and genomic data were retrospectively analyzed, and phenotypes were standardized using Human Phenotype Ontology (HPO) terms. Variants were classified per ACMG/ClinGen guidelines, and we assessed phenotypic burden, predictors of molecular diagnosis, copy number variants (CNVs), and functional convergence of candidate genes. A molecular diagnosis was identified in 112 patients (12.2%), including 82 with variants in ASD-associated genes or regions and 30 with findings related to other clinical features. We identified 16 novel pathogenic/likely pathogenic variants, along with 10 CNVs. Among trio-based patients, 70.9% of molecular diagnoses were de novo. Higher phenotypic burden was associated with molecular diagnosis, and global developmental delay was the strongest predictor after correction for multiple testing. Functional enrichment analysis of candidate genes showed convergence on pathways related to neuronal development, synaptic function, and ion transport. These findings highlight the genetic and phenotypic heterogeneity of ASD and support the value of integrating standardized genomic and phenotypic characterization in Colombian populations.
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BibTeX
@article{gutierrez2026phenotypic,
title = {{Phenotypic Complexity and Diagnostic Utility of Exome Sequencing in ASD: Real-World Insights from Colombia}},
author = {Diego Alejandro Rodríguez Gutiérrez and Ronald Cárdenas Prieto and Paula Rueda-Gaitán and Natalia Gomez-Lopera and Carlos Estrada-Serrato and Mario Isaza-Ruget and Juan Javier López Rivera},
journal = {International journal of molecular sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27198902},
url = {https://europepmc.org/article/PMC/PMC13665253},
note = {CC BY},
}
RIS
TY - JOUR
TI - Phenotypic Complexity and Diagnostic Utility of Exome Sequencing in ASD: Real-World Insights from Colombia
AU - Diego Alejandro Rodríguez Gutiérrez
AU - Ronald Cárdenas Prieto
AU - Paula Rueda-Gaitán
AU - Natalia Gomez-Lopera
AU - Carlos Estrada-Serrato
AU - Mario Isaza-Ruget
AU - Juan Javier López Rivera
PY - 2026
DA - 2026/10/01
JO - International journal of molecular sciences
DO - 10.3390/ijms27198902
UR - https://europepmc.org/article/PMC/PMC13665253
AB - Autism spectrum disorder (ASD) is a genetically heterogeneous condition; however, genomic data from Latin American populations remain limited. We investigated the molecular and phenotypic landscape of ASD in 916 Colombian patients who underwent whole-exome sequencing (WES) between 2022 and 2025. Clinical and genomic data were retrospectively analyzed, and phenotypes were standardized using Human Phenotype Ontology (HPO) terms. Variants were classified per ACMG/ClinGen guidelines, and we assessed phenotypic burden, predictors of molecular diagnosis, copy number variants (CNVs), and functional convergence of candidate genes. A molecular diagnosis was identified in 112 patients (12.2%), including 82 with variants in ASD-associated genes or regions and 30 with findings related to other clinical features. We identified 16 novel pathogenic/likely pathogenic variants, along with 10 CNVs. Among trio-based patients, 70.9% of molecular diagnoses were de novo. Higher phenotypic burden was associated with molecular diagnosis, and global developmental delay was the strongest predictor after correction for multiple testing. Functional enrichment analysis of candidate genes showed convergence on pathways related to neuronal development, synaptic function, and ion transport. These findings highlight the genetic and phenotypic heterogeneity of ASD and support the value of integrating standardized genomic and phenotypic characterization in Colombian populations.
SN - 1422-0067
ER -