INVESTIGAÇÃO GENÔMICA E EPIGENÉTICA DO AUTISMO EM INDIVÍDUOS COM E SEM ALTAS HABILIDADES: UMA ABORDAGEM INTEGRATIVA

Abstract

Autism Spectrum Disorder (ASD) is characterized by broad phenotypic
variability, ranging from significant impairments to exceptional cognitive abilities. This
study aimed to identify genomic and epigenetic markers associated with ASD in
individuals with and without high abilities, thereby contributing to the understanding
of its heterogeneity and guiding personalized interventions. We employed an
exploratory‑descriptive approach in three stages: (1) a systematic literature review
on ASD genetics and epigenetics; (2) selection of genes from the SFARI Gene
database with strong associations to synaptogenesis and neural development (e.g.,
MECP2, NRXN1, SHANK3); and (3) analysis of DNA methylation data reported in
scientific publications, seeking alterations in the preselected genes and identifying
new candidates (KDM5B, BCL11A). Our results indicate that individuals with ASD
often exhibit enhanced cognitive abilities in specific domains alongside deficits in
others, supporting the “high imbalance of intelligence” hypothesis. Canonical ASD
genes (SHANK3, NRXN1, NLGN3, CNTNAP2) confirmed their roles in synaptic
function and neuronal connectivity, while KDM5B and BCL11A emerged as additional
potential epigenetic regulators. We conclude that integrating genomic and epigenetic
data holds promise for identifying biomarkers that can improve ASD diagnosis and
prognosis and inform epigenetic‑targeted interventions. Future studies should
experimentally validate these signatures (e.g., ChIP‑seq, methylation arrays) and
assess their stability across development.