Genetic Traces in Autism Spectrum Disorders: A Whole Exome Sequencing Study from Türkiye

Area of Science:

• Genetics
• Neurodevelopmental disorders
• Molecular diagnostics

Background:

• Autism spectrum disorders (ASDs) are complex neurodevelopmental conditions characterized by social interaction deficits.
• Clinical diagnosis of ASD can be challenging due to symptom variability.
• Molecular genetic testing, including whole exome sequencing (WES), is crucial for accurate ASD diagnosis.

Purpose of the Study:

• To identify disease-related genetic variants in Turkish patients diagnosed with ASD using WES.
• To contribute population-specific variant data for ASD genetic research.
• To assess the utility of WES in a cohort of ASD patients negative for Fragile X syndrome.

Main Methods:

• Whole exome sequencing (WES) was performed on 75 pediatric patients diagnosed with ASD (DSM-5 criteria).
• Patients had normal results from Fragile X testing, cytogenetic analysis, and molecular karyotyping.
• Variant analysis focused on identifying pathogenic, likely pathogenic, and variants of unknown significance (VUS).

Main Results:

• Pathogenic or likely pathogenic (LP) variants were identified in 24% of ASD patients.
• Variants of unknown significance (VUS) were found in 45.3% of cases.
• The most frequently implicated genes were MECP2, EP300, and PTEN; four novel de novo variants were discovered in KMT2C, MECP2, PTEN, and TRRAP.

Conclusions:

• WES is a valuable tool for genetic diagnosis of ASD, aiding in etiology confirmation and personalized treatment strategies.
• Identifying gene and variant spectra across diverse populations, like the Turkish cohort studied, is critical for advancing ASD research.
• The discovery of novel variants underscores the ongoing importance of comprehensive genetic testing in ASD.