Comprehensive mtDNA variant analysis in Turkish pediatric ASD cohort
Background: Autism Spectrum Disorder (ASD) has a strong genetic basis, yet specific etiological factors remain unidentified in the majority of cases. Mitochondrial DNA (mtDNA) variations have been hypothesized as potential contributors to ASD development. However, the precise role of mtDNA remains unclear due to inconsistent findings across studies, which often suffer from methodological limitations. Aims: To comprehensively investigate the association between mtDNA variants, gene-level variant burden, and haplogroup distributions in a Turkish pediatric ASD cohort. Study Design: Case control study. Methods: Whole mtDNA analysis of peripheral blood samples from 95 children with ASD and 95 healthy controls was performed using next-generation sequencing. Identified variations were evaluated for pathogenicity via genomic databases and in silico analyses. Potentially pathogenic variations underwent segregation analysis. Additionally, mtDNA haplogroup distributions were compared between the groups. Results: The overall frequency of mtDNA variants was significantly higher in the ASD group than in the control group (p = 0.033). The ASD cohort harbored 23 distinct variants (initially classified as 3 pathogenic/likely pathogenic (P/LP) and 20 VUS); while the control group had 13 VUS and no P/LP variants.