Özücer, İpek Kuşcu; Alnak, Alper; Akköprü, Hilal; Karadoğan, Zeynep Nur; Çağlayan, Ahmet Okay; Selman, Saliha B.; Coskun, Murat

Background: Trimethyllysine Hydroxylase, Epsilon (TMLHE) gene mutations have been clinically associated with an increased risk of autism spectrum disorder (ASD). This study aimed to evaluate the peripheral expression profile of the TMLHE gene and its association with ASD phenotype in a clinical sample of youth diagnosed with ASD. Methods: The study sample included 205 participants (ASD: n = 100; controls: n = 105, Mage = 9.25 years, SD = 3.74). The Childhood Autism Rating Scale and the Aberrant Behavior Checklist were administered to assess the severity of ASD and associated symptoms. Peripheral blood samples were collected from all participants, and TMLHE gene expression levels were analyzed using quantitative reverse transcription PCR (RT-qPCR). Results: TMLHE gene expression was significantly downregulated in the ASD group compared to controls (p < .001). Notably, significant correlations were identified between TMLHE expression levels and the CARS subscales for object use (p = .043) and listening response (p = .038). Conclusion: This study represents the first case-control investigation of peripheral TMLHE gene expression in ASD, revealing that TMLHE expression is reduced in children with ASD compared to typically developing peers. These findings contribute to a deeper understanding of the potential implications of TMLHE gene mutations in the etiology of ASD.